Recognition of fibrinogen by leukocyte integrins.
Numerous studies have provided evidence that fibrinogen plays a multifaceted role in the immune and inflammatory response. The ability of fibrinogen to participate in the inflammatory response depends on its specific interaction with leukocyte cell surface adhesion receptors, integrins. Two leukocyte integrins, alpha M beta 2 (CD11b/CD18, Mac-1) and alpha X beta 2 (CD11c/CD18, p150,95), are the main fibrinogen receptors expressed on neutrophils, monocytes, macrophages and several subsets of lymphocytes. The recognition site for alpha M beta 2 has been previously mapped to the carboxyl-terminal globular gamma C domains (gamma 143-411) and two sequences, gamma 190-202 (P1) and gamma 377-395 (P2), were implicated as the putative binding sites. We now demonstrate that a second leukocyte integrin, alpha X beta 2, which is highly homologous to alpha M beta 2, mediates adhesion of the alpha X beta 2-bearing cells to the D fragment and to the recombinant gamma-module, gamma 143-411. Within the gamma C domain, alpha X beta 2 may recognize P1 and P2 sequences since synthetic peptides duplicating these sequences effectively inhibits adhesion of the alpha X beta 2-expressing cells to the D fragment. In addition, neutrophil inhibitory factor, NIF, a potent inhibitor of alpha X beta 2, also inhibited alpha X beta 2-mediated cell adhesion. These data suggest that recognition of the gamma C domain of fibrinogen by alpha M beta 2 and alpha X beta 2 may have common structural requirements.
Ugarova
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J.J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. ugarovt@ccf.org
Yakubenko
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D000818:Animals; D001704:Biopolymers; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D001704:Biopolymers; D016023:Integrins; D005340:Fibrinogen