A mitogenic action for fibrinogen mediated through intercellular adhesion molecule-1.
Intercellular adhesion molecule-1 (ICAM-1) is a cell surface ligand for alphaLbeta2 and alphaMbeta2 integrins and has a key role in leukocyte adhesion to the vascular endothelium. The plasma protein fibrinogen has also been shown to interact with ICAM-1. We have investigated the effect of fibrinogen binding to ICAM-1-expressing cells on cell proliferation. The inclusion of 200-800 nM fibrinogen but not fibronectin to the culture medium of Raji induced a 2-4-fold increase in [3H]thymidine incorporation after 8 h. Cell proliferation in cultures containing fibrinogen was also confirmed by direct cell counting. The proliferative response in Raji was abrogated by an anti-ICAM-1 mAb 84H10 which maps to the first Ig domain of ICAM-1. A purified truncated form of ICAM-1 containing the first two Ig-like domains and a peptide with amino acid sequence corresponding to ICAM-1 (8-22) was also able to block the proliferative action of fibrinogen on Raji. 200 nM fibrinogen induced a 3-fold increase in [3H]thymidine incorporation by 293 cells transfected with ICAM-1 cDNA but not control non-transfected 293 cells. Comparable mitogenic effects were achieved with fibrinogen fragments X and D100, and with a synthetic peptide with an amino acid sequence matching fibrinogen gamma chain (117-133). These results indicate that interaction between discrete sequences within ICAM-1 and fibrinogen result in cellular proliferation.
Gardiner
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Joseph J. Jacobs Center for Thrombosis, and Vascular Biology/FF-2, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
D'Souza
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D000595:Amino Acid Sequence; D002460:Cell Line; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D014162:Transfection
D007136:Immunoglobulins; D008934:Mitogens; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen