Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent
| Autor: | Paul F. Bradfield, Pilar Alcaide, Charles A. Parkos, Tony W. Liang, Beat A. Imhof, Monica Sircar, Deanna J. Lamont, Francis W. Luscinskas, Richard J. Fish, Gail Newton, Michel Aurrand-Lions, Lin Yang, Tanya N. Mayadas, Seema Sehrawat |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Antigens CD18/metabolism Neutrophils Interleukin-1beta Membrane Proteins/antagonists & inhibitors/immunology/ metabolism ddc:616.07 Lentivirus Infections/immunology Mice Cell Movement Immunology and Allergy Antigens CD31/drug effects/metabolism Immunoglobulins/immunology/ metabolism biology Chemistry Cell Adhesion Molecules/antagonists & inhibitors/immunology/ metabolism Antibodies Monoclonal Cell migration Adhesion Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1/drug effects/metabolism humanities Cell biology Endothelial stem cell Platelet Endothelial Cell Adhesion Molecule-1 Tumor Necrosis Factor-alpha/pharmacology cardiovascular system Shear Strength Junctional Adhesion Molecule C Intracellular education Immunology Integrin Immunoglobulins Proinflammatory cytokine Interleukin-1beta/pharmacology Antibodies Blocking/pharmacology Cell Adhesion Animals Cell adhesion Antibodies Blocking Tumor Necrosis Factor-alpha fungi Membrane Proteins Neutrophils/drug effects/ immunology Lipopolysaccharides/pharmacology Antibodies Monoclonal/pharmacology CD18 Antigens biology.protein Lentivirus Infections Cell Adhesion Molecules |
| Zdroj: | Journal of Immunology, Vol. 178, No 9 (2007) pp. 5879-5887 |
| ISSN: | 0022-1767 |
| Popis: | Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-α, IL-1β, or LPS did not increase its surface expression as assessed by FACS analysis. By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell junctions on resting or cytokine-activated HUVEC. Surprisingly, staining of detergent-permeabilized HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebrand factor. Adhesion studies in an in vitro flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration. Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or extent of transmigration of PMN or evoke a role for JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal role, if any, in PMN transmigration in this model and that ICAM-1 is the preferred endothelial-expressed ligand for PMN β2 integrins during transendothelial migration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|