Protease Inhibitors in Tick Saliva: The Role of Serpins and Cystatins in Tick-host-Pathogen Interaction
Jazyk angličtina Země Švýcarsko Médium electronic-ecollection
Typ dokumentu časopisecké články, přehledy, práce podpořená grantem
PubMed
28611951
PubMed Central
PMC5447049
DOI
10.3389/fcimb.2017.00216
Knihovny.cz E-zdroje
- Klíčová slova
- cystatins, immunomodulation, protease inhibitors, serpins, tick-host interaction,
- MeSH
- cystatiny fyziologie terapeutické užití MeSH
- imunomodulace MeSH
- inhibitory proteas klasifikace metabolismus terapeutické užití MeSH
- inhibitory serinových proteinas fyziologie terapeutické užití MeSH
- interakce hostitele a parazita MeSH
- klíšťata metabolismus MeSH
- lidé MeSH
- serpiny fyziologie terapeutické užití MeSH
- sliny enzymologie metabolismus MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cystatiny MeSH
- inhibitory proteas MeSH
- inhibitory serinových proteinas MeSH
- serpiny MeSH
The publication of the first tick sialome (salivary gland transcriptome) heralded a new era of research of tick protease inhibitors, which represent important constituents of the proteins secreted via tick saliva into the host. Three major groups of protease inhibitors are secreted into saliva: Kunitz inhibitors, serpins, and cystatins. Kunitz inhibitors are anti-hemostatic agents and tens of proteins with one or more Kunitz domains are known to block host coagulation and/or platelet aggregation. Serpins and cystatins are also anti-hemostatic effectors, but intriguingly, from the translational perspective, also act as pluripotent modulators of the host immune system. Here we focus especially on this latter aspect of protease inhibition by ticks and describe the current knowledge and data on secreted salivary serpins and cystatins and their role in tick-host-pathogen interaction triad. We also discuss the potential therapeutic use of tick protease inhibitors.
Faculty of Science University of South Bohemia in České BudějoviceČeské Budějovice Czechia
Institute of Parasitology Biology Center Czech Academy of SciencesČeské Budějovice Czechia
Zobrazit více v PubMed
Amara U., Rittirsch D., Flierl M., Bruckner U., Klos A., Gebhard F., et al. . (2008). Interaction between the coagulation and complement system. Adv. Exp. Med. Biol. 632, 71–79. 10.1007/978-0-387-78952-1_6 PubMed DOI PMC
Anguita J., Ramamoorthi N., Hovius J. W., Das S., Thomas V., Persinski R., et al. . (2002). Salp15, an ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity 16, 849–859. 10.1016/S1074-7613(02)00325-4 PubMed DOI
Ayllon N., Villar M., Galindo R. C., Kocan K. M., Sima R., Lopez J. A., et al. . (2015). Systems biology of tissue-specific response to Anaplasma phagocytophilum reveals differentiated apoptosis in the tick vector Ixodes scapularis. PLoS Genet. 11:e1005120. 10.1371/journal.pgen.1005120 PubMed DOI PMC
Bania J., Stachowiak D., Polanowski A. (1999). Primary structure and properties of the cathepsin G/chymotrypsin inhibitor from the larval hemolymph of Apis mellifera. Eur. J. Biochem. 262, 680–687. 10.1046/j.1432-1327.1999.00406.x PubMed DOI
Belorgey D., Hagglof P., Karlsson-Li S., Lomas D. A. (2007). Protein misfolding and the serpinopathies. Prion 1, 15–20. 10.4161/pri.1.1.3974 PubMed DOI PMC
Bot I., Shi G. P., Kovanen P. T. (2015). Mast cells as effectors in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 35, 265–271. 10.1161/ATVBAHA.114.303570 PubMed DOI PMC
Brossard M., Wikel S. K. (2004). Tick immunobiology. Parasitology 129 (Suppl.), S161–S176. 10.1017/S0031182004004834 PubMed DOI
Calvo E., Mizurini D. M., Sa-Nunes A., Ribeiro J. M., Andersen J. F., Mans B. J., et al. . (2011). Alboserpin, a factor Xa inhibitor from the mosquito vector of yellow fever, binds heparin and membrane phospholipids and exhibits antithrombotic activity. J. Biol. Chem. 286, 27998–28010. 10.1074/jbc.M111.247924 PubMed DOI PMC
Carrell R. W., Read R. J. (2016). How serpins transport hormones and regulate their release. Semin. Cell Dev. Biol. 62, 133–141. 10.1016/j.semcdb.2016.12.007 PubMed DOI
Caughey G. H. (2016). Mast cell proteases as pharmacological targets. Eur. J. Pharmacol. 778, 44–55. 10.1016/j.ejphar.2015.04.045 PubMed DOI PMC
Chalaire K. C., Kim T. K., Garcia-Rodriguez H., Mulenga A. (2011). Amblyomma americanum (L.) (Acari: Ixodidae) tick salivary gland serine protease inhibitor (serpin) 6 is secreted into tick saliva during tick feeding. J. Exp. Biol. 214, 665–673. 10.1242/jeb.052076 PubMed DOI PMC
Chen G., Wang X., Severo M. S., Sakhon O. S., Sohail M., Brown L. J., et al. . (2014). The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation during Anaplasma phagocytophilum infection. Infect. Immun. 82, 2553–2564. 10.1128/IAI.01679-14 PubMed DOI PMC
Chen Q., Fei J., Wu L., Jiang Z., Wu Y., Zheng Y., et al. . (2011). Detection of cathepsin B, cathepsin L, cystatin C, urokinase plasminogen activator and urokinase plasminogen activator receptor in the sera of lung cancer patients. Oncol. Lett. 2, 693–699. 10.3892/ol.2011.302 PubMed DOI PMC
Cherniack E. P. (2011). Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders. Altern. Med. Rev. 16, 50–58. PubMed
Chmelar J., Calvo E., Pedra J. H., Francischetti I. M., Kotsyfakis M. (2012). Tick salivary secretion as a source of antihemostatics. J. Proteomics 75, 3842–3854. 10.1016/j.jprot.2012.04.026 PubMed DOI PMC
Chmelar J., Kotal J., Kopecky J., Pedra J. H., Kotsyfakis M. (2016). All for one and one for all on the tick-host battlefield. Trends Parasitol. 32, 368–377. 10.1016/j.pt.2016.01.004 PubMed DOI PMC
Chmelar J., Oliveira C. J., Rezacova P., Francischetti I. M., Kovarova Z., Pejler G., et al. . (2011). A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation. Blood 117, 736–744. 10.1182/blood-2010-06-293241 PubMed DOI PMC
Colinet D., Dubuffet A., Cazes D., Moreau S., Drezen J. M., Poirie M. (2009). A serpin from the parasitoid wasp Leptopilina boulardi targets the Drosophila phenoloxidase cascade. Dev. Comp. Immunol. 33, 681–689. 10.1016/j.dci.2008.11.013 PubMed DOI
Corral-Rodriguez M. A., Macedo-Ribeiro S., Barbosa Pereira P. J., Fuentes-Prior P. (2009). Tick-derived Kunitz-type inhibitors as antihemostatic factors. Insect Biochem. Mol. Biol. 39, 579–595. 10.1016/j.ibmb.2009.07.003 PubMed DOI
Cox J. L. (2009). Cystatins and cancer. Front. Biosci. (Landmark Ed) 14, 463–474. 10.2741/3255 PubMed DOI
Dai S. X., Zhang A. D., Huang J. F. (2012). Evolution, expansion and expression of the Kunitz/BPTI gene family associated with long-term blood feeding in Ixodes Scapularis. BMC Evol. Biol. 12:4. 10.1186/1471-2148-12-4 PubMed DOI PMC
Davis R. L., Shrimpton A. E., Holohan P. D., Bradshaw C., Feiglin D., Collins G. H., et al. . (1999). Familial dementia caused by polymerization of mutant neuroserpin. Nature 401, 376–379. 10.1038/43894 PubMed DOI
Denhardt D. T., Greenberg A. H., Egan S. E., Hamilton R. T., Wright J. A. (1987). Cysteine proteinase cathepsin L expression correlates closely with the metastatic potential of H-ras-transformed murine fibroblasts. Oncogene 2, 55–59. PubMed
Di Cesare Mannelli L., Micheli L., Cinci L., Maresca M., Vergelli C., Pacini A., et al. . (2016). Effects of the neutrophil elastase inhibitor EL-17 in rat adjuvant-induced arthritis. Rheumatology (Oxford) 55, 1285–1294. 10.1093/rheumatology/kew055 PubMed DOI PMC
Ekeowa U. I., Gooptu B., Belorgey D., Hagglof P., Karlsson-Li S., Miranda E., et al. . (2009). alpha1-Antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies. Clin. Sci. 116, 837–850. 10.1042/CS20080484 PubMed DOI
El Rayes T., Catena R., Lee S., Stawowczyk M., Joshi N., Fischbach C., et al. . (2015). Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. Proc. Natl. Acad. Sci. U.S.A. 112, 16000–16005. 10.1073/pnas.1507294112 PubMed DOI PMC
Fogaca A. C., Almeida I. C., Eberlin M. N., Tanaka A. S., Bulet P., Daffre S. (2006). Ixodidin, a novel antimicrobial peptide from the hemocytes of the cattle tick Boophilus microplus with inhibitory activity against serine proteinases. Peptides 27, 667–674. 10.1016/j.peptides.2005.07.013 PubMed DOI
Frazao B., Vasconcelos V., Antunes A. (2012). Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview. Mar. Drugs 10, 1812–1851. 10.3390/md10081812 PubMed DOI PMC
Grosskinsky S., Schott M., Brenner C., Cutler S. J., Simon M. M., Wallich R. (2010). Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of Borrelia recurrentis. PLoS Negl. Trop. Dis. 4:e698. 10.1371/journal.pntd.0000698 PubMed DOI PMC
Grunclova L., Horn M., Vancova M., Sojka D., Franta Z., Mares M., et al. . (2006). Two secreted cystatins of the soft tick Ornithodoros moubata: differential expression pattern and inhibitory specificity. Biol. Chem. 387, 1635–1644. 10.1515/BC.2006.204 PubMed DOI
Guay C., Laviolette M., Tremblay G. M. (2006). Targeting serine proteases in asthma. Curr. Top. Med. Chem. 6, 393–402. 10.2174/156802606776287054 PubMed DOI
Gulia-Nuss M., Nuss A. B., Meyer J. M., Sonenshine D. E., Roe R. M., Waterhouse R. M., et al. . (2016). Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nat. Commun. 7:10507. 10.1038/ncomms10507 PubMed DOI PMC
Gulley M. M., Zhang X., Michel K. (2013). The roles of serpins in mosquito immunology and physiology. J. Insect Physiol. 59, 138–147. 10.1016/j.jinsphys.2012.08.015 PubMed DOI PMC
Hahn I., Klaus A., Janze A. K., Steinwede K., Ding N., Bohling J., et al. . (2011). Cathepsin G and neutrophil elastase play critical and nonredundant roles in lung-protective immunity against Streptococcus pneumoniae in mice. Infect. Immun. 79, 4893–4901. 10.1128/IAI.05593-11 PubMed DOI PMC
Haile W. B., Coleman J. L., Benach J. L. (2006). Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response. Cell. Microbiol. 8, 1349–1360. 10.1111/j.1462-5822.2006.00717.x PubMed DOI
Halangk W., Lerch M. M., Brandt-Nedelev B., Roth W., Ruthenbuerger M., Reinheckel T., et al. . (2000). Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J. Clin. Invest. 106, 773–781. 10.1172/JCI9411 PubMed DOI PMC
Han N., Jin K., He K., Cao J., Teng L. (2011). Protease-activated receptors in cancer: a systematic review. Oncol. Lett. 2, 599–608. 10.3892/ol.2011.291 PubMed DOI PMC
Hap A., Kielan W., Grzebieniak Z., Siewinski M., Rudnicki J., Tarnawa R., et al. . (2011). Control of active B and L cathepsins in tissues of colorectal cancer using cystatins isolated from chicken egg proteins: in vitro studies. Folia Histochem. Cytobiol. 49, 670–676. 10.5603/FHC.2011.0075 PubMed DOI
Heit C., Jackson B. C., Mcandrews M., Wright M. W., Thompson D. C., Silverman G. A., et al. . (2013). Update of the human and mouse SERPIN gene superfamily. Hum. Genomics 7:22. 10.1186/1479-7364-7-22 PubMed DOI PMC
Horka H., Staudt V., Klein M., Taube C., Reuter S., Dehzad N., et al. . (2012). The tick salivary protein sialostatin L inhibits the Th9-derived production of the asthma-promoting cytokine IL-9 and is effective in the prevention of experimental asthma. J. Immunol. 188, 2669–2676. 10.4049/jimmunol.1100529 PubMed DOI PMC
Horn M., Nussbaumerova M., Sanda M., Kovarova Z., Srba J., Franta Z., et al. . (2009). Hemoglobin digestion in blood-feeding ticks: mapping a multipeptidase pathway by functional proteomics. Chem. Biol. 16, 1053–1063. 10.1016/j.chembiol.2009.09.009 PubMed DOI PMC
Huntington J. A., Li W. (2009). Structural insights into the multiple functions of protein C inhibitor. Cell. Mol. Life Sci. 66, 113–121. 10.1007/s00018-008-8371-0 PubMed DOI PMC
Ibelli A. M., Hermance M. M., Kim T. K., Gonzalez C. L., Mulenga A. (2013). Bioinformatics and expression analyses of the Ixodes scapularis tick cystatin family. Exp. Appl. Acarol. 60, 41–53. 10.1007/s10493-012-9613-2 PubMed DOI PMC
Ibelli A. M., Kim T. K., Hill C. C., Lewis L. A., Bakshi M., Miller S., et al. . (2014). A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting. Int. J. Parasitol. 44, 369–379. 10.1016/j.ijpara.2014.01.010 PubMed DOI PMC
Imamura S., Da Silva Vaz Junior I., Sugino M., Ohashi K., Onuma M. (2005). A serine protease inhibitor (serpin) from Haemaphysalis longicornis as an anti-tick vaccine. Vaccine 23, 1301–1311. 10.1016/j.vaccine.2004.08.041 PubMed DOI
Imamura S., Konnai S., Vaz Ida S., Yamada S., Nakajima C., Ito Y., et al. . (2008). Effects of anti-tick cocktail vaccine against Rhipicephalus appendiculatus. Jpn. J. Vet. Res. 56, 85–98. 10.14943/jjvr.56.2.85 PubMed DOI
Imamura S., Konnai S., Yamada S., Parizi L. F., Githaka N., Vaz Ida S., Jr., et al. . (2013). Identification and partial characterization of a gut Rhipicephalus appendiculatus cystatin. Ticks Tick Borne Dis. 4, 138–144. 10.1016/j.ttbdis.2012.11.001 PubMed DOI
Imamura S., Namangala B., Tajima T., Tembo M. E., Yasuda J., Ohashi K., et al. . (2006). Two serine protease inhibitors (serpins) that induce a bovine protective immune response against Rhipicephalus appendiculatus ticks. Vaccine 24, 2230–2237. 10.1016/j.vaccine.2005.10.055 PubMed DOI
Jin C., Flavell R. A. (2010). Molecular mechanism of NLRP3 inflammasome activation. J. Clin. Immunol. 30, 628–631. 10.1007/s10875-010-9440-3 PubMed DOI
Jittapalapong S., Kaewhom P., Pumhom P., Canales M., De La Fuente J., Stich R. W. (2010). Immunization of rabbits with recombinant serine protease inhibitor reduces the performance of adult female Rhipicephalus microplus. Transbound. Emerg. Dis. 57, 103–106. 10.1111/j.1865-1682.2010.01108.x PubMed DOI
Kaewhom P., Sirinarumitr T., Chantakru S., Jittapalapong S. (2007). Cloning and characterization of cDNA encoding a serine protease inhibitor from salivary glands of thai cattle tick (Boophilus microplus). Kasetsart J. (Nat. Sci.) 41, 74–80.
Kanost M. R. (1999). Serine proteinase inhibitors in arthropod immunity. Dev. Comp. Immunol. 23, 291–301. 10.1016/S0145-305X(99)00012-9 PubMed DOI
Karim S., Miller N. J., Valenzuela J., Sauer J. R., Mather T. N. (2005). RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding. Biochem. Biophys. Res. Commun. 334, 1336–1342. 10.1016/j.bbrc.2005.07.036 PubMed DOI
Karim S., Ribeiro J. M. (2015). An Insight into the Sialome of the Lone Star Tick, Amblyomma americanum, with a Glimpse on its time dependent gene expression. PLoS ONE 10:e0131292. 10.1371/journal.pone.0131292 PubMed DOI PMC
Karim S., Singh P., Ribeiro J. M. (2011). A deep insight into the sialotranscriptome of the gulf coast tick, Amblyomma maculatum. PLoS ONE 6:e28525. 10.1371/journal.pone.0028525 PubMed DOI PMC
Kawada A., Hara K., Kominami E., Hiruma M., Noguchi H., Ishibashi A. (1997). Processing of cathepsins L, B and D in psoriatic epidermis. Arch. Dermatol. Res. 289, 87–93. 10.1007/s004030050160 PubMed DOI
Kazimirova M., Stibraniova I. (2013). Tick salivary compounds: their role in modulation of host defences and pathogen transmission. Front. Cell. Infect. Microbiol. 3:43. 10.3389/fcimb.2013.00043 PubMed DOI PMC
Kennedy B., Gargoum F. S., Kennedy L., Khan F., Curran D. R., O'connor T. M. (2012). Emerging anticoagulants. Curr. Med. Chem. 19, 3388–3416. 10.2174/092986712801215847 PubMed DOI
Kessenbrock K., Krumbholz M., Schonermarck U., Back W., Gross W. L., Werb Z., et al. . (2009). Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15, 623–625. 10.1038/nm.1959 PubMed DOI PMC
Kim H. S., Krege J. H., Kluckman K. D., Hagaman J. R., Hodgin J. B., Best C. F., et al. . (1995). Genetic control of blood pressure and the angiotensinogen locus. Proc. Natl. Acad. Sci. U.S.A. 92, 2735–2739. 10.1073/pnas.92.7.2735 PubMed DOI PMC
Kim T. K., Radulovic Z., Mulenga A. (2016). Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19. Ticks Tick Borne Dis. 7, 405–414. 10.1016/j.ttbdis.2015.12.017 PubMed DOI PMC
Kim T. K., Tirloni L., Radulovic Z., Lewis L., Bakshi M., Hill C., et al. . (2015). Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions. Int. J. Parasitol. 45, 613–627. 10.1016/j.ijpara.2015.03.009 PubMed DOI PMC
Klein M., Bruhl T. J., Staudt V., Reuter S., Grebe N., Gerlitzki B., et al. . (2015). Tick salivary sialostatin L represses the initiation of immune responses by targeting IRF4-dependent transcription in murine mast cells. J. Immunol. 195, 621–631. 10.4049/jimmunol.1401823 PubMed DOI PMC
Kopitar-Jerala N. (2012). The role of cysteine proteinases and their inhibitors in the host-pathogen cross talk. Curr. Protein Pept. Sci. 13, 767–775. 10.2174/138920312804871102 PubMed DOI PMC
Kordis D., Turk V. (2009). Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes. BMC Evol. Biol. 9:266. 10.1186/1471-2148-9-266 PubMed DOI PMC
Kos J., Mitrovic A., Mirkovic B. (2014). The current stage of cathepsin B inhibitors as potential anticancer agents. Future Med. Chem. 6, 1355–1371. 10.4155/fmc.14.73 PubMed DOI
Kotsyfakis M., Anderson J. M., Andersen J. F., Calvo E., Francischetti I. M., Mather T. N., et al. . (2008). Cutting edge: immunity against a “silent” salivary antigen of the Lyme vector Ixodes scapularis impairs its ability to feed. J. Immunol. 181, 5209–5212. 10.4049/jimmunol.181.8.5209 PubMed DOI PMC
Kotsyfakis M., Horka H., Salat J., Andersen J. F. (2010). The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model. Mol. Microbiol. 77, 456–470. 10.1111/j.1365-2958.2010.07220.x PubMed DOI PMC
Kotsyfakis M., Karim S., Andersen J. F., Mather T. N., Ribeiro J. M. (2007). Selective cysteine protease inhibition contributes to blood-feeding success of the tick Ixodes scapularis. J. Biol. Chem. 282, 29256–29263. 10.1074/jbc.M703143200 PubMed DOI
Kotsyfakis M., Kopacek P., Franta Z., Pedra J. H., Ribeiro J. M. (2015a). Deep Sequencing Analysis of the Ixodes ricinus Haemocytome. PLoS Negl. Trop. Dis. 9:e0003754. 10.1371/journal.pntd.0003754 PubMed DOI PMC
Kotsyfakis M., Sa-Nunes A., Francischetti I. M., Mather T. N., Andersen J. F., Ribeiro J. M. (2006). Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis. J. Biol. Chem. 281, 26298–26307. 10.1074/jbc.M513010200 PubMed DOI
Kotsyfakis M., Schwarz A., Erhart J., Ribeiro J. M. (2015b). Tissue- and time-dependent transcription in Ixodes ricinus salivary glands and midguts when blood feeding on the vertebrate host. Sci. Rep. 5:9103. 10.1038/srep09103 PubMed DOI PMC
Kovarova Z., Chmelar J., Sanda M., Brynda J., Mares M., Rezacova P. (2010). Crystallization and diffraction analysis of the serpin IRS-2 from the hard tick Ixodes ricinus. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66, 1453–1457. 10.1107/S1744309110032343 PubMed DOI PMC
Kuester D., Lippert H., Roessner A., Krueger S. (2008). The cathepsin family and their role in colorectal cancer. Pathol. Res. Pract. 204, 491–500. 10.1016/j.prp.2008.04.010 PubMed DOI
Law R. H., Zhang Q., Mcgowan S., Buckle A. M., Silverman G. A., Wong W., et al. . (2006). An overview of the serpin superfamily. Genome Biol. 7:216. 10.1186/gb-2006-7-5-216 PubMed DOI PMC
Leboulle G., Crippa M., Decrem Y., Mejri N., Brossard M., Bollen A., et al. . (2002a). Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. J. Biol. Chem. 277, 10083–10089. 10.1074/jbc.M111391200 PubMed DOI
Leboulle G., Rochez C., Louahed J., Ruti B., Brossard M., Bollen A., et al. . (2002b). Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding. Am. J. Trop. Med. Hyg. 66, 225–233. 10.4269/ajtmh.2002.66.225 PubMed DOI
Li J., Zhang C., Xu X., Wang J., Yu H., Lai R., et al. . (2007). Trypsin inhibitory loop is an excellent lead structure to design serine protease inhibitors and antimicrobial peptides. FASEB J. 21, 2466–2473. 10.1096/fj.06-7966com PubMed DOI
Lieskovska J., Palenikova J., Langhansova H., Campos Chagas A., Calvo E., Kotsyfakis M., et al. . (2015a). Tick sialostatins L and L2 differentially influence dendritic cell responses to Borrelia spirochetes. Parasit. Vectors 8:275. 10.1186/s13071-015-0887-1 PubMed DOI PMC
Lieskovska J., Palenikova J., Sirmarova J., Elsterova J., Kotsyfakis M., Campos Chagas A., et al. . (2015b). Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells. Parasite Immunol. 37, 70–78. 10.1111/pim.12162 PubMed DOI
Lima C. A., Sasaki S. D., Tanaka A. S. (2006). Bmcystatin, a cysteine proteinase inhibitor characterized from the tick Boophilus microplus. Biochem. Biophys. Res. Commun. 347, 44–50. 10.1016/j.bbrc.2006.06.018 PubMed DOI
Lima L. G., Monteiro R. Q. (2013). Activation of blood coagulation in cancer: implications for tumour progression. Biosci. Rep. 33:pii: e00064. 10.1042/BSR20130057 PubMed DOI PMC
Liu J., Sukhova G. K., Yang J. T., Sun J., Ma L., Ren A., et al. . (2006). Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells. Atherosclerosis 184, 302–311. 10.1016/j.atherosclerosis.2005.05.012 PubMed DOI
Liu X. Y., De La Fuente J., Cote M., Galindo R. C., Moutailler S., Vayssier-Taussat M., et al. . (2014). IrSPI, a tick serine protease inhibitor involved in tick feeding and Bartonella henselae infection. PLoS Negl. Trop. Dis. 8:e2993. 10.1371/journal.pntd.0002993 PubMed DOI PMC
Lomas D. A., Hurst J. R., Gooptu B. (2016). Update on alpha-1 antitrypsin deficiency: new therapies. J. Hepatol. 65, 413–424. 10.1016/j.jhep.2016.03.010 PubMed DOI
Lu H., Cassis L. A., Kooi C. W., Daugherty A. (2016). Structure and functions of angiotensinogen. Hypertens. Res. 39, 492–500. 10.1038/hr.2016.17 PubMed DOI PMC
Lu S., Soares T. S., Vaz Junior I. S., Lovato D. V., Tanaka A. S. (2014). Rmcystatin3, a cysteine protease inhibitor from Rhipicephalus microplus hemocytes involved in immune response. Biochimie 106, 17–23. 10.1016/j.biochi.2014.07.012 PubMed DOI
Mansuy-Aubert V., Zhou Q. L., Xie X., Gong Z., Huang J. Y., Khan A. R., et al. . (2013). Imbalance between neutrophil elastase and its inhibitor alpha1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 17, 534–548. 10.1016/j.cmet.2013.03.005 PubMed DOI PMC
Maritz-Olivier C., Stutzer C., Jongejan F., Neitz A. W., Gaspar A. R. (2007). Tick anti-hemostatics: targets for future vaccines and therapeutics. Trends Parasitol. 23, 397–407. 10.1016/j.pt.2007.07.005 PubMed DOI
Meekins D. A., Kanost M. R., Michel K. (2017). Serpins in arthropod biology. Semin. Cell Dev. Biol. 62, 105–119. 10.1016/j.semcdb.2016.09.001 PubMed DOI PMC
Miyata J., Tani K., Sato K., Otsuka S., Urata T., Lkhagvaa B., et al. . (2007). Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant. Rheumatol Int. 27, 375–382. 10.1007/s00296-006-0210-8 PubMed DOI
Moreira H. N., Barcelos R. M., Vidigal P. M., Klein R. C., Montandon C. E., Maciel T. E., et al. . (2017). A deep insight into the whole transcriptome of midguts, ovaries and salivary glands of the Amblyomma sculptum tick. Parasitol. Int. 66, 64–73. 10.1016/j.parint.2016.10.011 PubMed DOI
Mulenga A., Blandon M., Khumthong R. (2007a). The molecular basis of the Amblyomma americanum tick attachment phase. Exp. Appl. Acarol. 41, 267–287. 10.1007/s10493-007-9064-3 PubMed DOI
Mulenga A., Khumthong R., Blandon M. A. (2007b). Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins. J. Exp. Biol. 210, 3188–3198. 10.1242/jeb.006494 PubMed DOI
Mulenga A., Khumthong R., Chalaire K. C. (2009). Ixodes scapularis tick serine proteinase inhibitor (serpin) gene family; annotation and transcriptional analysis. BMC Genomics 10:217. 10.1186/1471-2164-10-217 PubMed DOI PMC
Mulenga A., Khumthong R., Chalaire K. C., Strey O., Teel P. (2008). Molecular and biological characterization of the Amblyomma americanum organic anion transporter polypeptide. J. Exp. Biol. 211, 3401–3408. 10.1242/jeb.022376 PubMed DOI
Mulenga A., Kim T., Ibelli A. M. (2013). Amblyomma americanum tick saliva serine protease inhibitor 6 is a cross-class inhibitor of serine proteases and papain-like cysteine proteases that delays plasma clotting and inhibits platelet aggregation. Insect. Mol. Biol. 22, 306–319. 10.1111/imb.12024 PubMed DOI PMC
Mulenga A., Tsuda A., Onuma M., Sugimoto C. (2003). Four serine proteinase inhibitors (serpin) from the brown ear tick, Rhiphicephalus appendiculatus; cDNA cloning and preliminary characterization. Insect Biochem. Mol. Biol. 33, 267–276. 10.1016/S0965-1748(02)00240-0 PubMed DOI
Muller S., Dennemarker J., Reinheckel T. (2012). Specific functions of lysosomal proteases in endocytic and autophagic pathways. Biochim. Biophys. Acta 1824, 34–43. 10.1016/j.bbapap.2011.07.003 PubMed DOI PMC
Nickel W. (2003). The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes. Eur. J. Biochem. 270, 2109–2119. 10.1046/j.1432-1033.2003.03577.x PubMed DOI
Niles J. L., Mccluskey R. T., Ahmad M. F., Arnaout M. A. (1989). Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood 74, 1888–1893. PubMed
Ooi C. P., Haines L. R., Southern D. M., Lehane M. J., Acosta-Serrano A. (2015). Tsetse GmmSRPN10 has anti-complement activity and is important for successful establishment of trypanosome infections in the fly midgut. PLoS Negl. Trop. Dis. 9:e3448. 10.1371/journal.pntd.0003448 PubMed DOI PMC
Owen C. A. (2008). Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 3, 253–268. 10.2147/COPD.S2089 PubMed DOI PMC
Pal U., Li X., Wang T., Montgomery R. R., Ramamoorthi N., Desilva A. M., et al. . (2004). TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell 119, 457–468. 10.1016/j.cell.2004.10.027 PubMed DOI
Palenikova J., Lieskovska J., Langhansova H., Kotsyfakis M., Chmelar J., Kopecky J. (2015). Ixodes ricinus salivary serpin IRS-2 affects Th17 differentiation via inhibition of the interleukin-6/STAT-3 signaling pathway. Infect. Immun. 83, 1949–1956. 10.1128/IAI.03065-14 PubMed DOI PMC
Parizi L. F., Sabadin G. A., Alzugaray M. F., Seixas A., Logullo C., Konnai S., et al. . (2015). Rhipicephalus microplus and Ixodes ovatus cystatins in tick blood digestion and evasion of host immune response. Parasit. Vectors 8:122. 10.1186/s13071-015-0743-3 PubMed DOI PMC
Pejler G., Ronnberg E., Waern I., Wernersson S. (2010). Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115, 4981–4990. 10.1182/blood-2010-01-257287 PubMed DOI
Perner J., Provaznik J., Schrenkova J., Urbanova V., Ribeiro J. M., Kopacek P. (2016). RNA-seq analyses of the midgut from blood- and serum-fed Ixodes ricinus ticks. Sci. Rep. 6:36695. 10.1038/srep36695 PubMed DOI PMC
Pham C. T. (2006). Neutrophil serine proteases: specific regulators of inflammation. Nat. Rev. Immunol. 6, 541–550. 10.1038/nri1841 PubMed DOI
Pham C. T. (2008). Neutrophil serine proteases fine-tune the inflammatory response. Int. J. Biochem. Cell Biol. 40, 1317–1333. 10.1016/j.biocel.2007.11.008 PubMed DOI PMC
Pierre P., Mellman I. (1998). Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 93, 1135–1145. 10.1016/S0092-8674(00)81458-0 PubMed DOI
Pislar A., Kos J. (2014). Cysteine cathepsins in neurological disorders. Mol. Neurobiol. 49, 1017–1030. 10.1007/s12035-013-8576-6 PubMed DOI
Porter L. M., Radulovic Z. M., Mulenga A. (2017). A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses. Parasit. Vectors 10:152. 10.1186/s13071-017-2080-1 PubMed DOI PMC
Porter L., Radulovic Z., Kim T., Braz G. R., Da Silva Vaz I., Jr., Mulenga A. (2015). Bioinformatic analyses of male and female Amblyomma americanum tick expressed serine protease inhibitors (serpins). Ticks Tick Borne Dis. 6, 16–30. 10.1016/j.ttbdis.2014.08.002 PubMed DOI PMC
Prevot P. P., Adam B., Boudjeltia K. Z., Brossard M., Lins L., Cauchie P., et al. . (2006). Anti-hemostatic effects of a serpin from the saliva of the tick Ixodes ricinus. J. Biol. Chem. 281, 26361–26369. 10.1074/jbc.M604197200 PubMed DOI
Prevot P. P., Beschin A., Lins L., Beaufays J., Grosjean A., Bruys L., et al. . (2009). Exosites mediate the anti-inflammatory effects of a multifunctional serpin from the saliva of the tick Ixodes ricinus. FEBS J. 276, 3235–3246. 10.1111/j.1742-4658.2009.07038.x PubMed DOI
Prevot P. P., Couvreur B., Denis V., Brossard M., Vanhamme L., Godfroid E. (2007). Protective immunity against Ixodes ricinus induced by a salivary serpin. Vaccine 25, 3284–3292. 10.1016/j.vaccine.2007.01.008 PubMed DOI
Quinn D. J., Weldon S., Taggart C. C. (2010). Antiproteases as therapeutics to target inflammation in cystic fibrosis. Open Respir. Med. J. 4, 20–31. 10.2174/1874306401004010020 PubMed DOI PMC
Rangel C. K., Parizi L. F., Sabadin G. A., Costa E. P., Romeiro N. C., Isezaki M., et al. . (2017). Molecular and structural characterization of novel cystatins from the taiga tick Ixodes persulcatus. Ticks Tick Borne Dis. 8, 432–441. 10.1016/j.ttbdis.2017.01.007 PubMed DOI
Rawlings N. D., Barrett A. J. (1990). Evolution of proteins of the cystatin superfamily. J. Mol. Evol. 30, 60–71. 10.1007/BF02102453 PubMed DOI
Rawlings N. D., Salvesen G. (2013). Handbook of Proteolytic Enzymes, 3rd Edn. London; Boston: Academic Press.
Ribeiro J. M., Slovak M., Francischetti I. M. (2017). An insight into the sialome of Hyalomma excavatum. Ticks Tick Borne Dis. 8, 201–207. 10.1016/j.ttbdis.2016.08.011 PubMed DOI PMC
Rimphanitchayakit V., Tassanakajon A. (2010). Structure and function of invertebrate Kazal-type serine proteinase inhibitors. Dev. Comp. Immunol. 34, 377–386. 10.1016/j.dci.2009.12.004 PubMed DOI
Rodriguez-Valle M., Vance M., Moolhuijzen P. M., Tao X., Lew-Tabor A. E. (2012). Differential recognition by tick-resistant cattle of the recombinantly expressed Rhipicephalus microplus serine protease inhibitor-3 (RMS-3). Ticks Tick Borne Dis. 3, 159–169. 10.1016/j.ttbdis.2012.03.002 PubMed DOI
Rodriguez-Valle M., Xu T., Kurscheid S., Lew-Tabor A. E. (2015). Rhipicephalus microplus serine protease inhibitor family: annotation, expression and functional characterisation assessment. Parasit. Vectors 8:7. 10.1186/s13071-014-0605-4 PubMed DOI PMC
Salát J., Paesen G. C., Rezácová P., Kotsyfakis M., Kovárová Z., Sanda M., et al. . (2010). Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata. Biochem. J. 429, 103–112. 10.1042/BJ20100280 PubMed DOI PMC
Sandhaus R. A., Turino G. (2013). Neutrophil elastase-mediated lung disease. COPD 10 (Suppl. 1), 60–63. 10.3109/15412555.2013.764403 PubMed DOI
Sa-Nunes A., Bafica A., Antonelli L. R., Choi E. Y., Francischetti I. M., Andersen J. F., et al. . (2009). The immunomodulatory action of sialostatin L on dendritic cells reveals its potential to interfere with autoimmunity. J. Immunol. 182, 7422–7429. 10.4049/jimmunol.0900075 PubMed DOI PMC
Sasaki S. D., De Lima C. A., Lovato D. V., Juliano M. A., Torquato R. J., Tanaka A. S. (2008). BmSI-7, a novel subtilisin inhibitor from Boophilus microplus, with activity toward Pr1 proteases from the fungus Metarhizium anisopliae. Exp. Parasitol. 118, 214–220. 10.1016/j.exppara.2007.08.003 PubMed DOI
Scherer H. U., Dorner T., Burmester G. R. (2010). Patient-tailored therapy in rheumatoid arthritis: an editorial review. Curr. Opin. Rheumatol. 22, 237–245. 10.1097/BOR.0b013e328337b832 PubMed DOI
Schmitt E., Germann T., Goedert S., Hoehn P., Huels C., Koelsch S., et al. . (1994). IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma. J. Immunol. 153, 3989–3996. PubMed
Schwarz A., Cabezas-Cruz A., Kopecky J., Valdes J. J. (2014). Understanding the evolutionary structural variability and target specificity of tick salivary Kunitz peptides using next generation transcriptome data. BMC Evol. Biol. 14:4. 10.1186/1471-2148-14-4 PubMed DOI PMC
Schwarz A., Valdes J. J., Kotsyfakis M. (2012). The role of cystatins in tick physiology and blood feeding. Ticks Tick Borne Dis. 3, 117–127. 10.1016/j.ttbdis.2012.03.004 PubMed DOI PMC
Schwarz A., Von Reumont B. M., Erhart J., Chagas A. C., Ribeiro J. M., Kotsyfakis M. (2013). De novo Ixodes ricinus salivary gland transcriptome analysis using two next-generation sequencing methodologies. FASEB J. 27, 4745–4756. 10.1096/fj.13-232140 PubMed DOI PMC
Shapiro S. D. (2002). Proteinases in chronic obstructive pulmonary disease. Biochem. Soc. Trans. 30, 98–102. 10.1042/bst0300098 PubMed DOI
Shi X., Gangadharan B., Brass L. F., Ruf W., Mueller B. M. (2004). Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis. Mol. Cancer Res. 2, 395–402. Available online at: http://mcr.aacrjournals.org/content/2/7/395.article-info PubMed
Silverman G. A., Whisstock J. C., Bottomley S. P., Huntington J. A., Kaiserman D., Luke C. J., et al. . (2010). Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems. J. Biol. Chem. 285, 24299–24305. 10.1074/jbc.R110.112771 PubMed DOI PMC
Stark K. R., James A. A. (1995). A factor Xa-directed anticoagulant from the salivary glands of the yellow fever mosquito Aedes aegypti. Exp. Parasitol. 81, 321–331. 10.1006/expr.1995.1123 PubMed DOI
Stark K. R., James A. A. (1998). Isolation and characterization of the gene encoding a novel factor Xa-directed anticoagulant from the yellow fever mosquito, Aedes aegypti. J. Biol. Chem. 273, 20802–20809. 10.1074/jbc.273.33.20802 PubMed DOI
Steinwede K., Maus R., Bohling J., Voedisch S., Braun A., Ochs M., et al. . (2012). Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in mice. J. Immunol. 188, 4476–4487. 10.4049/jimmunol.1103346 PubMed DOI
Stephenson E., Savvatis K., Mohiddin S. A., Marelli-Berg F. M. (2016). T-cell immunity in myocardial inflammation: pathogenic role and therapeutic manipulation. Br. J. Pharmacol. 10.1111/bph.13613 PubMed DOI PMC
Sudhan D. R., Siemann D. W. (2015). Cathepsin L targeting in cancer treatment. Pharmacol. Ther. 155, 105–116. 10.1016/j.pharmthera.2015.08.007 PubMed DOI PMC
Sugino M., Imamura S., Mulenga A., Nakajima M., Tsuda A., Ohashi K., et al. . (2003). A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis longicornis; cloning and preliminary assessment of its suitability as a candidate for a tick vaccine. Vaccine 21, 2844–2851. 10.1016/S0264-410X(03)00167-1 PubMed DOI
Sun J., Sukhova G. K., Wolters P. J., Yang M., Kitamoto S., Libby P., et al. . (2007). Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat. Med. 13, 719–724. 10.1038/nm1601 PubMed DOI
Sun J., Zhang J., Lindholt J. S., Sukhova G. K., Liu J., He A., et al. . (2009). Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation. Circulation 120, 973–982. 10.1161/CIRCULATIONAHA.109.849679 PubMed DOI PMC
Takeda A., Jimi T., Wakayama Y., Misugi N., Miyake S., Kumagai T. (1992). Demonstration of cathepsins B, H and L in xenografts of normal and Duchenne-muscular-dystrophy muscles transplanted into nude mice. Biochem. J. 288 (Pt 2), 643–648. 10.1042/bj2880643 PubMed DOI PMC
Talukdar S., Oh D. Y., Bandyopadhyay G., Li D., Xu J., Mcnelis J., et al. . (2012). Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med. 18, 1407–1412. 10.1038/nm.2885 PubMed DOI PMC
Tan G. J., Peng Z. K., Lu J. P., Tang F. Q. (2013). Cathepsins mediate tumor metastasis. World J. Biol. Chem. 4, 91–101. 10.4331/wjbc.v4.i4.91 PubMed DOI PMC
Tang H. (2009). Regulation and function of the melanization reaction in Drosophila. Fly (Austin) 3, 105–111. 10.4161/fly.3.1.7747 PubMed DOI
Tirloni L., Kim T. K., Coutinho M. L., Ali A., Seixas A., Termignoni C., et al. . (2016). The putative role of Rhipicephalus microplus salivary serpins in the tick-host relationship. Insect. Biochem. Mol. Biol. 71, 12–28. 10.1016/j.ibmb.2016.01.004 PubMed DOI PMC
Tirloni L., Reck J., Terra R. M., Martins J. R., Mulenga A., Sherman N. E., et al. . (2014a). Proteomic analysis of cattle tick Rhipicephalus (Boophilus) microplus saliva: a comparison between partially and fully engorged females. PLoS ONE 9:e94831. 10.1371/journal.pone.0094831 PubMed DOI PMC
Tirloni L., Seixas A., Mulenga A., Vaz Ida S., Jr., Termignoni C. (2014b). A family of serine protease inhibitors (serpins) in the cattle tick Rhipicephalus (Boophilus) microplus. Exp. Parasitol. 137, 25–34. 10.1016/j.exppara.2013.12.001 PubMed DOI
Toyomane K., Konnai S., Niwa A., Githaka N., Isezaki M., Yamada S., et al. . (2016). Identification and the preliminary in vitro characterization of IRIS homologue from salivary glands of Ixodes persulcatus Schulze. Ticks Tick Borne Dis. 7, 119–125. 10.1016/j.ttbdis.2015.09.006 PubMed DOI
Tumminello F. M., Leto G., Pizzolanti G., Candiloro V., Crescimanno M., Crosta L., et al. . (1996). Cathepsin D, B and L circulating levels as prognostic markers of malignant progression. Anticancer Res. 16, 2315–2319. PubMed
Turk V., Stoka V., Vasiljeva O., Renko M., Sun T., Turk B., et al. . (2012). Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824, 68–88. 10.1016/j.bbapap.2011.10.002 PubMed DOI PMC
Twigg M. S., Brockbank S., Lowry P., Fitzgerald S. P., Taggart C., Weldon S. (2015). The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung. Mediators Inflamm. 2015:293053. 10.1155/2015/293053 PubMed DOI PMC
Valdes J. J., Moal I. H. (2014). Prediction of Kunitz ion channel effectors and protease inhibitors from the Ixodes ricinus sialome. Ticks Tick Borne Dis. 5, 947–950. 10.1016/j.ttbdis.2014.07.016 PubMed DOI
Valenzuela J. G., Francischetti I. M., Pham V. M., Garfield M. K., Mather T. N., Ribeiro J. M. (2002). Exploring the sialome of the tick Ixodes scapularis. J. Exp. Biol. 205, 2843–2864. Available online at: http://jeb.biologists.org/content/205/18/2843.article-info PubMed
Wagner C. J., Schultz C., Mall M. A. (2016). Neutrophil elastase and matrix metalloproteinase 12 in cystic fibrosis lung disease. Mol Cell Pediatr 3:25. 10.1186/s40348-016-0053-7 PubMed DOI PMC
Wang Y., Yu X., Cao J., Zhou Y., Gong H., Zhang H., et al. . (2015a). Characterization of a secreted cystatin from the tick Rhipicephalus haemaphysaloides. Exp. Appl. Acarol. 67, 289–298. 10.1007/s10493-015-9946-8 PubMed DOI
Wang Y., Zhou Y., Gong H., Cao J., Zhang H., Li X., et al. . (2015b). Functional characterization of a cystatin from the tick Rhipicephalus haemaphysaloides. Parasit. Vectors 8:140. 10.1186/s13071-015-0725-5 PubMed DOI PMC
Whisstock J. C., Silverman G. A., Bird P. I., Bottomley S. P., Kaiserman D., Luke C. J., et al. . (2010). Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. J. Biol. Chem. 285, 24307–24312. 10.1074/jbc.R110.141408 PubMed DOI PMC
Wikel S. (2013). Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment. Front. Microbiol. 4:337. 10.3389/fmicb.2013.00337 PubMed DOI PMC
Willadsen P., Bird P., Cobon G. S., Hungerford J. (1995). Commercialisation of a recombinant vaccine against Boophilus microplus. Parasitology 110 (Suppl.), S43–S50. 10.1017/S0031182000001487 PubMed DOI
Xu T., Lew-Tabor A., Rodriguez-Valle M. (2016). Effective inhibition of thrombin by Rhipicephalus microplus serpin-15 (RmS-15) obtained in the yeast Pichia pastoris. Ticks Tick Borne Dis. 7, 180–187. 10.1016/j.ttbdis.2015.09.007 PubMed DOI
Yamaji K., Tsuji N., Miyoshi T., Hatta T., Alim M. A., Anisuzzaman, et al. . (2010). Hlcyst-1 and Hlcyst-2 are potential inhibitors of HlCPL-A in the midgut of the ixodid tick Haemaphysalis longicornis. J. Vet. Med. Sci. 72, 599–604. 10.1292/jvms.09-0561 PubMed DOI
Yamaji K., Tsuji N., Miyoshi T., Islam M. K., Hatta T., Alim M. A., et al. . (2009a). Hemoglobinase activity of a cysteine protease from the ixodid tick Haemaphysalis longicornis. Parasitol. Int. 58, 232–237. 10.1016/j.parint.2009.05.003 PubMed DOI
Yamaji K., Tsuji N., Miyoshi T., Islam M. K., Hatta T., Alim M. A., et al. . (2009b). A salivary cystatin, HlSC-1, from the ixodid tick Haemaphysalis longicornis play roles in the blood-feeding processes. Parasitol. Res. 106, 61–68. 10.1007/s00436-009-1626-3 PubMed DOI
Yasuda Y., Kaleta J., Bromme D. (2005). The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv. Drug Deliv. Rev. 57, 973–993. 10.1016/j.addr.2004.12.013 PubMed DOI
Yu Y., Cao J., Zhou Y., Zhang H., Zhou J. (2013). Isolation and characterization of two novel serpins from the tick Rhipicephalus haemaphysaloides. Ticks Tick Borne Dis. 4, 297–303. 10.1016/j.ttbdis.2013.02.001 PubMed DOI
Zavasnik-Bergant T. (2008). Cystatin protease inhibitors and immune functions. Front. Biosci. 13, 4625–4637. 10.2741/3028 PubMed DOI
Zeng X. C., Liu Y., Shi W., Zhang L., Luo X., Nie Y., et al. . (2014). Genome-wide search and comparative genomic analysis of the trypsin inhibitor-like cysteine-rich domain-containing peptides. Peptides 53, 106–114. 10.1016/j.peptides.2013.08.012 PubMed DOI
Zhang J., Sun J., Lindholt J. S., Sukhova G. K., Sinnamon M., Stevens R. L., et al. . (2011). Mast cell tryptase deficiency attenuates mouse abdominal aortic aneurysm formation. Circ. Res. 108, 1316–1327. 10.1161/CIRCRESAHA.111.243758 PubMed DOI PMC
Zhou J., Liao M., Gong H., Xuan X., Fujisaki K. (2010). Characterization of Hlcyst-3 as a member of cystatins from the tick Haemaphysalis longicornis. Exp. Appl. Acarol. 51, 327–333. 10.1007/s10493-010-9336-1 PubMed DOI
Zhou J., Liao M., Hatta T., Tanaka M., Xuan X., Fujisaki K. (2006a). Identification of a follistatin-related protein from the tick Haemaphysalis longicornis and its effect on tick oviposition. Gene 372, 191–198. 10.1016/j.gene.2005.12.020 PubMed DOI
Zhou J., Liao M., Ueda M., Gong H., Xuan X., Fujisaki K. (2009). Characterization of an intracellular cystatin homolog from the tick Haemaphysalis longicornis. Vet. Parasitol. 160, 180–183. 10.1016/j.vetpar.2008.10.086 PubMed DOI
Zhou J., Ueda M., Umemiya R., Battsetseg B., Boldbaatar D., Xuan X., et al. . (2006b). A secreted cystatin from the tick Haemaphysalis longicornis and its distinct expression patterns in relation to innate immunity. Insect Biochem. Mol. Biol. 36, 527–535. 10.1016/j.ibmb.2006.03.003 PubMed DOI
Serpins in Tick Physiology and Tick-Host Interaction
Structural and biochemical characterization of the novel serpin Iripin-5 from Ixodes ricinus
Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement
Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite-Host Crosstalk
The Use of Tick Salivary Proteins as Novel Therapeutics
The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin