Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells.
Endothelial cells and activated platelets express integrin-type receptors responsible for adhesion to fibrinogen. We have located distinct integrin-directed endothelial cell and platelet attachment sites on immobilized fibrinogen using a combination of synthetic peptides, fibrinogen fragments, and specific anti-peptide monoclonal antibodies. Endothelial cells exclusively recognize an Arg-Gly-Asp-containing site near the C-terminus of the alpha chain (alpha residues 572-574) but fail to recognize the Arg-Gly-Asp sequence in the N-terminal region of the same chain (alpha residues 95-97). In contrast, platelets do not require either Arg-Gly-Asp sequence for binding to intact fibrinogen and are capable of recognizing, in addition to the alpha 572-574 sequence, a site at the C-terminus of the gamma chain (gamma residues 400-411). These data suggest a molecular mechanism whereby platelets and endothelial cells interact with distinct sites on the fibrinogen molecule during hemostasis and wound healing.
Cheresh
D A
DA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Berliner
S A
SA
Vicente
V
V
Ruggeri
Z M
ZM
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000502:physiology*; D001665:Binding Sites; D001792:Blood Platelets / Q000166:cytology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D004730:Endothelium, Vascular / Q000166:cytology*; D005340:Fibrinogen / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen