Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18).
Platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) is a member of the Ig gene superfamily expressed on the surfaces of monocytes (Mo), neutrophils (PMN), and some T cell subsets, as well as on platelets and the intercellular junctions of endothelial cells. We used mAbs (mAb) against PECAM on Mo and PMN to mimic interaction with natural ligand. Such treatment resulted in the rapid increase of leukocyte beta 2 integrin-mediated adhesive function, as measured in two in vitro assays. Anti-PECAM-treated Mo bound more rapidly and in a CD18-dependent manner to cultured endothelial cells. Monovalent Fab fragments augmented binding significantly and intact IgG, bivalent F(ab')2 fragments, and secondarily cross-linked Fab fragments were even more effective. In a direct assay of CD11b/CD18 (CR3) function, PMN settling on surfaces coated with anti-PECAM mAb (including Fab fragments) were stimulated to bind C3bi-coated erythrocytes. These studies demonstrate that, in addition to the previously described functions of PECAM-1, this molecule is capable of participating in an adhesion cascade resulting in the activation of Mo and PMN beta 2 integrins. This activation may be important for the CR3-dependent adhesion events that are critical in the emigration of Mo and PMN at sites of inflammation.
Berman
M E
ME
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Muller
W A
WA
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011485:Protein Binding; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1