Fibrinogen induces adhesion, spreading, and microfilament organization of human endothelial cells in vitro.
Human umbilical vein endothelial cells (ECs) have been shown to attach to a substratum of fibrinogen (fg). Later, ECs undergo spreading, organization of thick microfilament bundles of the stress fiber type, and formation of focal contacts (adhesion plaques) that correspond to accumulation of vinculin at the cytoplasmic aspect of the ventral membrane. The rate of attachment to fg and the type of spreading is virtually identical to that obtained on substrata coated with fibronectin (FN). Antibodies to fg, but not to FN, prevent EC adhesion to fg; conversely, antibodies to FN, but not to fg, prevent adhesion of ECs to a FN-coated substratum. The removal of residual FN contamination from fg preparations by means of DEAE-cellulose chromatography does not result in any difference in EC adhesion on fg. Moreover, pretreatment of cells with inhibitors of synthesis and release of proteins does not impair their adhesion capacity on an fg-coated substratum. In contrast, human arterial smooth muscle cells do not adhere and spread on fg substrata but do so on FN. The synthetic peptides (Gly-Arg-Gly-Asp[GRGD] and Gly-Arg-Gly-Asp-Ser-Pro[GRGDSP]) containing the tripeptide Arg-Gly-Asp (RGD), originally found to be responsible for the cell binding activity of FN, have been found to inhibit EC spreading and the redistribution of their cytoskeleton, including the formation of stress fibers and the localization of vinculin either on fg or on FN. Conversely, the synthetic peptide Arg-Gly-Gly (RGG) was completely uneffective in inhibiting the adhesion and the sequence of events leading to spreading and cytoskeletal organization. These results indicate that ECs, but not smooth muscle cells, specifically adhere and spread on an fg substratum and this occurs by recognition mechanisms similar to those reported for FN.
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D007611:Aprotinin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure*; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005340:Fibrinogen / Q000502:physiology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D014176:Protein Biosynthesis; D014471:Umbilical Veins / Q000166:cytology / Q000648:ultrastructure
D006629:Hirudins; D005340:Fibrinogen; D007611:Aprotinin