Fibrinogen-Endothelial Cell Interaction in Vitro: A Pathway Mediated by an Arg-Gly-Asp Recognition Specificity

It has been previously shown that fibrinogen (FG) associates specifically with human umbilical vein and bovine aortic endothelial cells (EC) in culture and induces EC migration. In the present study. we have investigated whether the FG-EC interaction is mediated by an Arg-GIy-Asp (RGD) recognition s...

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Bibliographic Details
Published in:Blood 1989-02, Vol.73 (3), p.734-742
Main Authors: Languino, L.R., Colella, S., Zanetti, A., Andrieux, A., Ryckewaert, J.J., Charon, M.H., Marchisio, P.C., Plow, E.F., Ginsberg, M.H., Marguerie, G., Dejana, E.
Format: Article
Language:English
Subjects:
Antigens, Surface - physiology
Biological and medical sciences
Blood coagulation. Blood cells
Cell Adhesion
Cell Adhesion Molecules
Cell Movement - drug effects
Coagulation factors
Endothelium, Vascular - physiology
Fibrinogen - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Immunologic Techniques
In Vitro Techniques
Molecular and cellular biology
Molecular Weight
Oligopeptides - pharmacology
Platelet Membrane Glycoproteins - immunology
Platelet Membrane Glycoproteins - metabolism
Receptors, Cell Surface - metabolism
Structure-Activity Relationship
Time Factors
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Summary:It has been previously shown that fibrinogen (FG) associates specifically with human umbilical vein and bovine aortic endothelial cells (EC) in culture and induces EC migration. In the present study. we have investigated whether the FG-EC interaction is mediated by an Arg-GIy-Asp (RGD) recognition specificity and whether EC membrane proteins related to platelet GPllb-IlIa are involved. Highly purified radioiodinated human FG. containing no detectable fibronectin. interacted with cultured human and bovine EC in suspension in a time-dependent and specific manner. The binding was inhibited by EDTA. Two polyclonal antibodies to platelet GPllb-Illa, which immunoprecipitated a heterodimer molecule from EC, inhibited FG binding to EC. These same antibodies inhibited FG-induced EC migration in a dose-dependent manner as measured in a Boyden chamber. Preabsorption of the antibodies with purified platelet GPIIb-lIla markedly reduced both inhibitory activities. A series of synthetic RGD-containing peptides inhibited FG binding to EC and FG-induced EC migration. GIy-Arg-GIy-Asp (GRGD) was the most active peptide tested in inhibiting FG binding and EC migration (IDe, of 30 gsM). and conservative substitutions in the RGD sequence markedly reduced inhibitory activity (lD50, ›1,000,μM). These results indicate that FG binding and EC migration are events mediated by an RGD recognition specificity and that EC surface proteins immunologically related to the GPlIb-lIIa complex on platelets are involved in this recognition.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V73.3.734.734