A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30796952
DOI
10.1016/j.ijpara.2018.11.010
PII: S0020-7519(19)30026-8
Knihovny.cz E-zdroje
- Klíčová slova
- Anticoagulant, Diplozoidae, Factor X, Haematophagy, Helminth, Kunitz, Peptidase inhibitor, Plasmin,
- MeSH
- antifibrinolytika chemie imunologie MeSH
- antikoagulancia chemie imunologie MeSH
- faktor Xa imunologie MeSH
- hemostáza * MeSH
- infekce červy třídy Trematoda krev imunologie parazitologie veterinární MeSH
- inhibitory enzymů chemie imunologie MeSH
- inhibitory faktoru Xa chemie imunologie MeSH
- interakce hostitele a parazita MeSH
- kapři krev imunologie parazitologie MeSH
- komplement imunologie MeSH
- nemoci ryb krev imunologie parazitologie MeSH
- plasmin imunologie MeSH
- plazmatický kalikrein antagonisté a inhibitory imunologie MeSH
- proteiny červů chemie genetika imunologie MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- Trematoda chemie genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antifibrinolytika MeSH
- antikoagulancia MeSH
- faktor Xa MeSH
- inhibitory enzymů MeSH
- inhibitory faktoru Xa MeSH
- komplement MeSH
- plasmin MeSH
- plazmatický kalikrein MeSH
- proteiny červů MeSH
Serine peptidases are involved in many physiological processes including digestion, haemostasis and complement cascade. Parasites regulate activities of host serine peptidases to their own benefit, employing various inhibitors, many of which belong to the Kunitz-type protein family. In this study, we confirmed the presence of potential anticoagulants in protein extracts of the haematophagous monogenean Eudiplozoon nipponicum which parasitizes the common carp. We then focused on a Kunitz protein (EnKT1) discovered in the E. nipponicum transcriptome, which structurally resembles textilinin-1, an antihemorrhagic snake venom factor from Pseudonaja textilis. The protein was recombinantly expressed, purified and biochemically characterised. The recombinant EnKT1 did inhibit in vitro activity of Factor Xa of the coagulation cascade, but exhibited a higher activity against plasmin and plasma kallikrein, which participate in fibrinolysis, production of kinins, and complement activation. Anti-coagulation properties of EnKT1 based on the inhibition of Factor Xa were confirmed by thromboelastography, but no effect on fibrinolysis was observed. Moreover, we discovered that EnKT1 significantly impairs the function of fish complement, possibly by inhibiting plasmin or Factor Xa which can act as a C3 and C5 convertase. We localised Enkt1 transcripts and protein within haematin digestive cells of the parasite by RNA in situ hybridisation and immunohistochemistry, respectively. Based on these results, we suggest that the secretory Kunitz protein of E. nipponicum has a dual function. In particular, it impairs both haemostasis and complement activation in vitro, and thus might facilitate digestion of a host's blood and protect a parasite's gastrodermis from damage by the complement. This study presents, to our knowledge, the first characterisation of a Kunitz protein from monogeneans and the first example of a parasite Kunitz inhibitor that impairs the function of the complement.
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