The structural motif glycine 190-valine 202 of the fibrinogen gamma chain interacts with CD11b/CD18 integrin (alpha M beta 2, Mac-1) and promotes leukocyte adhesion.

摘要: 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 3 or endothelial cell v integrins, interacts approximately 30-kDa plasmic fragment D (D30) of that lacks the Arg-Gly-Asp sequences in A chain carboxyl terminus gamma chain. Using epitope-mapped antibodies synthetic peptidyl mimicry, we have now identified unique linear sequence mediates ligand binding to CD11b/CD18. Anti-fibrinogen directed region 95-264 inhibited 125I-fibrinogen 125I-D30 chemoattractant-stimulated neutrophils monocytic THP-1 cells dose-dependent fashion. Partially overlapping peptides reproducing this were tested their ability inhibit leukocytes. peptide designated P1, duplicating Gly190-Val202, blocked adhesion these immobilized Increasing concentrations P1 isolated cell-free system. Consistent genuine 125I-P1 bound saturably reaction by molar excess unlabeled peptide, fibrinogen, D30. Finally, effectively supported CD11b/CD18-dependent manner. These data suggest Gly190-Val202 functions as minimal recognition leukocyte Given participation fibrinogen:leukocyte interaction inflammation atherogenesis, antagonists based structural motif would interfere aberrant mechanisms without affecting Arg-Gly-Asp-directed vascular integrins.