Fibronectin Binding to Thrombin-Stimulated Platelets: Evidence for Fibrin(ogen) Independent and Dependent Pathways

• Published in: Blood 1985-07, Vol.66 (1), p.26-32
• Main Authors: Plow, Edward F., Marguerie, Gerard A., Ginsberg, Mark H.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Binding, Competitive; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - metabolism; Cations, Divalent; Fibrin - blood; Fibrin - metabolism; Fibrinogen - blood; Fibrinogen - metabolism; Fibronectins - blood; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Molecular and cellular biology; Molecular Weight; Platelet; Thrombin - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V66.1.26.26

Plasma fibronectin binds in a specific and saturable manner to thrombin-stimulated platelets. 7-Thrombin stimulated 80% as much fibronectin binding to platelets as a-thrombin with conversion of ≤1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magne-sium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronec-tin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin-stimu-lated cells. Second, formaldehyde-fixed cells with surface-associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit crosslinked to the a-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-depen-dent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate. © 1985 by Grune & Stratton, Inc.