Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Because free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity-related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced 11 candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena. Suitable single nucleotide polymorphism markers of potential functional importance, located in genes coding for basigin (BSG, CD147), the signaling lymphocyte activating molecule (SLAMF1), the poliovirus-related receptor-4 (NECTIN4, PVRL4), toll-like receptors 3, 7, 8 (TLR3, TLR7, TLR8), natural resistance-associated macrophage protein (SLC11A1) and natural cytotoxicity triggering receptor 1 (NCR1), were identified in each model species, along with MHC-DQB haplotypes unique for each species. This set of molecular markers represents a potentially useful tool for studying host genetic variation and susceptibility to morbillivirus infection in Cetaceans as well as for studying functionally important genetic diversity of selected Cetacean populations.
- MeSH
- basigin genetika imunologie MeSH
- biologické markery metabolismus MeSH
- delfíni rodu Stenella genetika imunologie virologie MeSH
- exprese genu MeSH
- genetická predispozice k nemoci * MeSH
- histokompatibilita - antigeny třídy II genetika imunologie MeSH
- infekce viry z rodu Morbillivirus genetika imunologie virologie MeSH
- jednonukleotidový polymorfismus * MeSH
- molekuly buněčné adheze genetika imunologie MeSH
- Morbillivirus imunologie patogenita MeSH
- Phocoena genetika imunologie virologie MeSH
- proteiny přenášející kationty genetika imunologie MeSH
- receptor 1 spouštějící přirozenou cytotoxicitu genetika imunologie MeSH
- SLAMF1 protein genetika imunologie MeSH
- toll-like receptor 3 genetika imunologie MeSH
- toll-like receptor 7 genetika imunologie MeSH
- toll-like receptor 8 genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Periostin je matricelulární protein o m. h. 90 000, který byl poprvé prokázán v myších osteoblastech. Záhy byla doložena jeho přítomnosti u člověka. Svůj název získal díky vysoké expresi v periostu. Do povědomí pneumologů a alergologů se dostal především díky pracím prokazujícím závislost jeho produkce na stimulaci interleukiny 4 (IL-4) a 13 (IL-13) a transformujícím růstovým faktorem β (TGFβ). To otevřelo bránu k jeho využití jako biologickému znaku imunopatologických stavů spojených s jejich produkcí, a to zejména endotypu bronchiálního astmatu spojeného se zvýšenou aktivitou Th2 subsetu a idiopatické plicní fibrózy. V následujícím textu jsou shrnuty některé klíčové poznatky z více než 20 let výzkumu struktury a funkcí periostinu, který přivedl měření jeho sérové hladiny až do klinických studií.
Periostin is a 90kDa matricellular protein, first demonstrated in mouse osteoblasts. Soon after, its presence was demonstrated also in humans. It gained its name due to its high expression in the periosteum. The awareness of pulmonologists and allergists came primarily thr ough the works providing the dependence of its production on stimulation by interleukins 13 (IL-13) and 4 (IL-4) and by transforming growth factor β (TGFβ). This opened the gates to its use as a biomarker of immune pathological conditions associated with their overproduction, especia lly Th2 high asthma endotype and idiopathic pulmonary fibrosis. The following text summarizes some key lessons from about 20 years of resear ch of the structure and functions of periostin, which brought measuring its serum levels up to clinical trials.
- MeSH
- biologické markery MeSH
- bronchiální astma * diagnóza etiologie imunologie patofyziologie MeSH
- idiopatická plicní fibróza * diagnóza etiologie imunologie patofyziologie MeSH
- interleukin-13 imunologie MeSH
- interleukin-4 imunologie MeSH
- lidé MeSH
- molekuly buněčné adheze * diagnostické užití fyziologie imunologie MeSH
- transformující růstový faktor beta imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Monodisperse (4 μm) macroporous crosslinked poly(glycidyl methacrylate) (PGMA) microspheres for use in microfluidic immunomagnetic cell sorting, with a specific application to the capture of circulating tumor cells (CTCs), were prepared by multistep swelling polymerization in the presence of cyclohexyl acetate porogen and hydrolyzed and ammonolyzed. Iron oxide was then precipitated in the microspheres to render them magnetic. Repeated precipitation made possible to raise the iron oxide content to more than 30 wt %. To minimize nonspecific adsorption of the microspheres in a microchannel and of cells on the microspheres, they were coated with albumin crosslinked with glutaraldehyde. Antibodies of epithelial cell adhesion molecule (anti-EpCAM) were then immobilized on the albumin-coated magnetic microspheres using the carbodiimide method. Capture of breast cancer MCF7 cells as a model of CTCs by the microspheres with immobilized anti-EpCAM IgG was performed in a batch experiment. Finally, MCF7 cells were captured by the anti-EpCAM-immobilized albumin-coated magnetic microspheres in an Ephesia chip. A very good rejection of lymphocytes was achieved. Thus, albumin-coated monodisperse magnetic PGMA microspheres with immobilized anti-EpCAM seem to be promising for capture of CTCs in a microfluidic device.
- MeSH
- acetoacetáty chemie MeSH
- antigeny nádorové imunologie MeSH
- epitelové buňky účinky léků patologie MeSH
- hydrolýza účinky léků MeSH
- imobilizační protilátky farmakologie MeSH
- kyseliny polymethakrylové chemie MeSH
- lidé MeSH
- magnetické jevy * MeSH
- methakryláty chemie MeSH
- MFC-7 buňky MeSH
- mikrofluidní analytické techniky MeSH
- mikrosféry * MeSH
- mikroskopie elektronová rastrovací MeSH
- molekuly buněčné adheze imunologie MeSH
- nádory prsu patologie MeSH
- poréznost MeSH
- sérový albumin chemie MeSH
- spektrofotometrie infračervená MeSH
- železité sloučeniny chemie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mnohočetný myelom je hematoonkologické onemocnění charakterizované maligní proliferací plazmatických buněk. Tyto buňky se hromadí v kostní dřeni, kde potlačují fyziologickou krvetvorbu a zároveň interagují s celou škálou cytokinů, růstových faktorů a adhezivních molekul. Je zřejmé, že právě mikroprostředí kostní dřeně hraje velkou roli v patogenezi onemocnění, ale i v rezistenci k léčbě.
Multiple myeloma is a hematooncological disease characterized by malignant proliferation of plasma cells. These cells accumulate in the bone marrow where they suppress physiological hematopoiesis; at the same time, these cells interact with a wide variety of cytokines, growth factors and adhesion molecules. It is obvious that the bone marrow microenvironment plays an important role in disease pathogenesis as well as treatment resistance.
- Klíčová slova
- IL-6,
- MeSH
- 1-fosfatidylinositol-3-kinasa genetika imunologie účinky léků MeSH
- cytokiny genetika imunologie účinky léků MeSH
- faktory růstu hematopoetických buněk imunologie metabolismus účinky léků MeSH
- financování organizované MeSH
- hematopoéza genetika imunologie účinky léků MeSH
- Janus kinasa 2 genetika imunologie účinky léků MeSH
- kostní dřeň imunologie patologie MeSH
- léková rezistence genetika imunologie účinky léků MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy genetika imunologie účinky léků MeSH
- mnohočetný myelom diagnóza etiologie MeSH
- molekuly buněčné adheze imunologie metabolismus účinky léků MeSH
- NF-kappa B genetika imunologie účinky léků MeSH
- plazmatické buňky metabolismus patologie účinky léků MeSH
- ras proteiny genetika imunologie účinky léků MeSH
- signální dráha Wnt genetika imunologie účinky léků MeSH
- transkripční faktor STAT3 genetika imunologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Dendritic cells (DCs) are specific antigen-presenting cells that play critical roles in the initiation and polarization of immune responses. DCs residing in the lungs might be detected in the bronchoalveolar lavage fluid (BALF). We analysed DC compartment in the peripheral blood and BALF of patients with allergy and in controls. Plasmacytoid and four distinct subsets of myeloid DCs [characterized by the expression of blood dendritic cell antigen (BDCA)-1+ and -3+ and CD16 positivity or negativity] were detected in both tested compartments. We further evaluated the expression of C-type lectins [mannose receptor (MR), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and dendritic and epithelial cells (DEC)-205] relevant to the pathogenesis of asthma. Interestingly, we found a selective increase in the frequency of myeloid DC-expressing BDCA-3 and MR particularly in BALF from allergic patients. Specific and highly statistically significant increase in BDCA-3+ and/or MR+ DCs brings a novel characteristic to BAL analysis in allergic patients.
- MeSH
- bronchiální astma krev imunologie MeSH
- bronchoalveolární lavážní tekutina cytologie imunologie MeSH
- dendritické buňky cytologie imunologie MeSH
- dítě MeSH
- dospělí MeSH
- GPI-vázané proteiny krev imunologie MeSH
- imunofenotypizace metody MeSH
- lektiny typu C krev imunologie MeSH
- lidé MeSH
- molekuly buněčné adheze krev imunologie MeSH
- neparametrická statistika MeSH
- plíce cytologie imunologie MeSH
- průtoková cytometrie MeSH
- receptory buněčného povrchu krev imunologie MeSH
- receptory IgG krev imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Circulating tumor cells (CTCs) are potential precursors of metastasis. They are also of use in diagnosing malignancy and for prognostic purposes. Our laboratory has previously isolated CTCs from orthotopic nude mouse models of human prostate cancer cells where the PC-3 cancer cells express green fluorescent protein (GFP). It was found that orthotopic tumors produced CTCs and not subcutaneous tumors, which may explain why orthotopic tumors metastasize and subcutaneous tumors do not. However, in this previous study, CTCs were observed only after culture. In the present study, using the GFP-expressing PC-3 orthotopic model and immunomagnetic beads coated with anti-epithelial cell adhesion molecule (EpCAM) and anti-prostate specific membrane antigen (PSMA), GFP-expressing CTC were isolated within 15 minutes and were readily visualized by GFP fluorescence. It was possible to immediately place the immunomagnetic-bead-captured GFP-expressing PC-3 CTCs in 3-dimensional sponge cell culture, where they proliferated. The combination of GFP expression and the use of immunomagnetic beads is a very powerful method to obtain CTCs for either immediate analysis or for biological characterization in vivo or in 3-dimensional culture.
- MeSH
- antigeny nádorové imunologie MeSH
- glutamátkarboxypeptidasa II imunologie MeSH
- imunomagnetická separace MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- molekuly buněčné adheze imunologie MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádorové cirkulující buňky patologie MeSH
- nádory prostaty metabolismus patologie MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The aberrant expression of myeloid antigens on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon. So far, there have been no reports of a functional consequence of this aberrant expression. The granulocytic marker carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6, CD66c) is a GPI-anchored molecule that is reported to be the most frequently aberrantly expressed myeloid marker in ALL with a strong correlation with genotype. MATERIALS AND METHODS: We mimicked CEACAM6 signaling in ALL cells by cross-linking with anti-CEACAM6 antibody. Next, we measured a response to CEACAM6 signaling by integrin subunits expression, integrin ligand binding, phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), Akt, and p38 mitogen-activated protein kinase (MAPK) and apoptosis by flow cytometry. RESULTS: Following CEACAM6 cross-linking in ALL cells, we detected Erk1/2, Akt, and p38 MAPK phosphorylation and integrin upregulation, as well as enhanced binding of integrin ligands (vascular cell adhesion molecule-1 [VCAM-1] and intercellular cell adhesion molecule-1 [ICAM-1]). However, CEACAM6 signaling resulted in an increase in apoptosis, unlike other GPI-anchored molecules, such as CD24. CONCLUSION: The present study is the first to demonstrate the functional consequences of CEACAM6 cross-linking in B-cell precursor ALL cells.
- MeSH
- antigeny nádorové imunologie metabolismus MeSH
- apoptóza MeSH
- CD antigeny imunologie metabolismus MeSH
- fosforylace účinky léků imunologie MeSH
- GPI-vázané proteiny MeSH
- imunologický capping MeSH
- integriny imunologie metabolismus MeSH
- lidé MeSH
- MAP kinasový signální systém MeSH
- mezibuněčná adhezivní molekula-1 imunologie metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 imunologie metabolismus MeSH
- mitogenem aktivované proteinkinasy p38 imunologie metabolismus MeSH
- molekuly buněčné adheze antagonisté a inhibitory imunologie metabolismus MeSH
- nádorové buněčné linie MeSH
- onkogenní protein v-akt imunologie metabolismus MeSH
- pre-B-buněčná leukemie imunologie metabolismus MeSH
- protilátky nádorové imunologie farmakologie MeSH
- regulace genové exprese u leukemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We have previously shown that the heavy chains (HCs) of inter-alpha-trypsin inhibitor (IalphaI) become covalently linked to hyaluronan (HA) during in vivo and in vitro expansion of porcine oocyte-cumulus cell complexes (OCCs). We have now studied by immunoblotting the synthesis of tumor necrosis factor alpha-induced protein 6 (TNFAIP6), which is essential for catalyzing this reaction in expanding mouse OCCs. Expanding OCCs were collected from preovulatory follicles of naturally cycling pigs and also after in vitro culture (24 or 42 h) in medium supplemented with FSH and pig serum. After isolation, OCCs were treated with Streptomyces hyaluronidase or Chondroitinase ABC. Matrix, cell pellet, and total extracts were analyzed by Western blotting. A band of about 35 kDa and a doublet of about 120 kDa, corresponding to the molecular weight of the native and HC-linked forms of TNFAIP6, respectively, were detected by a rabbit anti-human TNFAIP6 polyclonal antibody in matrix extracts of expanded cumuli. Moreover, we found by using a cell-free assay that porcine follicular fluid collected from follicles at 24 h after hCG stimulation contains HC-HA coupling activity. This activity was abolished by the rat anti-human monoclonal antibody A38, which has an epitope within the Link module domain of TNFAIP6. These experiments suggest that free TNFAIP6 protein was present in follicular fluid aspirated from porcine follicles 24 h after hCG stimulation. In contrast to mouse, we show that the A38 monoclonal antibody does not affect in vitro cumulus expansion of porcine OCCs.
- MeSH
- alfa-globuliny metabolismus MeSH
- časové faktory MeSH
- epitopy metabolismus MeSH
- financování organizované MeSH
- folikulární fáze metabolismus MeSH
- folikulární tekutina metabolismus MeSH
- inbrední kmeny myší MeSH
- kultivované buňky MeSH
- kyselina hyaluronová metabolismus MeSH
- molekuly buněčné adheze imunologie metabolismus MeSH
- monoklonální protilátky farmakologie imunologie MeSH
- myši MeSH
- ovariální folikul cytologie metabolismus účinky léků MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- MeSH
- arterioskleróza etiologie imunologie MeSH
- cévní buněčněadhezivní molekula-1 imunologie MeSH
- cévní endotel účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- hyperglykemie imunologie MeSH
- mezibuněčná adhezivní molekula-1 imunologie MeSH
- molekuly buněčné adheze imunologie MeSH
- techniky in vitro MeSH
- venae umbilicales MeSH
