The Journal of biological chemistry
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The leukocyte-restricted integrin CD11b/CD18 (alpha M beta 2, Mac-1) is a receptor for fibrinogen on stimulated monocytes and neutrophils. At variance with platelet alpha IIb beta 3 or endothelial cell alpha v beta 3 integrins, CD11b/CD18 interacts with a approximately 30-kDa plasmic fragment D (D30) of fibrinogen that lacks the Arg-Gly-Asp sequences in the A alpha chain and the carboxyl terminus of the gamma chain. Using epitope-mapped antibodies and synthetic peptidyl mimicry, we have now identified a unique linear sequence in fibrinogen that mediates ligand binding to CD11b/CD18. ⋯ Finally, immobilized P1 effectively supported adhesion of THP-1 cells in a CD11b/CD18-dependent manner. These data suggest that the fibrinogen gamma chain region Gly190-Val202 functions as a minimal recognition sequence for the leukocyte integrin CD11b/CD18. Given the participation of fibrinogen:leukocyte interaction in inflammation and atherogenesis, antagonists based on this unique structural motif would effectively interfere with aberrant leukocyte adhesion mechanisms without affecting Arg-Gly-Asp-directed vascular integrins.