Fibroblasts spread on immobilized fibrin monomer by mobilizing a β₁- class integrin, together with a vitronectin receptor α(v)β₃ on their surface

Human and murine fibroblasts were found to spread far more avidly on fibrin monomer monolayers than on immobilized fibrinogen, indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin- mediated augmentation of cell spreading. In fact, cell spreading was not efficiently augmented on monolayers of a thrombin-treated dysfibrinogen lacking the release of fibrinopeptide A due to an Aα Arg-16 → Cys substitution. Since a synthetic Arg-Gly-Asp (RGD)-containing peptide inhibited the fibrin-mediated cell spreading, subsequent dissociation of the carboxyl-terminal globular domain of the Aα-chains appears to render the RGD segments accessible to the cell-surface integrins. In support of this, fibrin-augmented cell spreading was inhibited by an antibody recognizing a 12-kDa peptide segment with γ Met-89 at its amino terminus, which is located in close association with the RGD segment at Aα 95-97 in the helical coiled- coil inter-domainal connector. The fibrin-mediated augmentation of cell spreading was inhibited not only by an antibody against human vitronectin receptor (LM 609) but also by an antibody against the β₁ subunit of integrin (mAb13), suggesting that the β₁-class integrin together with a vitronectin receptor, α(v)β₃, is mobilized onto the surface of fibroblasts upon contact with the fibrin monomer monolayer.