Thrombospondin binds to monocytes-macrophages and mediates platelet-monocyte adhesion.
Thrombospondin (TSP) is a multifunctional platelet glycoprotein synthesized by a variety of cells in culture including monocytes and macrophages. We now report that 125I-TSP binds specifically, saturably, and reversibly to mouse peritoneal macrophages and to cells of the monocyte-like human cell line U937 with dissociation constants of 6.7-14.5 X 10(-8) M and 3-4 X 10(5) binding sites per cell. TSP mediates an adhesive interaction between thrombin-stimulated platelets and both U937 cells and human blood monocytes. Using a sensitive rosetting assay, we found that monocytes were not rosetted by resting platelets whereas greater than 90% were rosetted by thrombin-stimulated platelets. Monoclonal and polyclonal anti-TSP antibodies markedly inhibited rosetting as did TSP itself. Neither control antibodies nor heparin, fibronectin, fibrinogen, nor the fibronectin adhesion tetrapeptide Arg-Gly-Asp-Ser inhibited rosetting. TSP may thus serve as a molecular bridge linking activated platelets with monocytes at sites of early vascular injury. Such interaction may be of critical importance in the regulation of thrombosis and the initiation of atherosclerosis.
D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion; D002460:Cell Line; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D012397:Rosette Formation; D013917:Thrombin / Q000494:pharmacology; D019699:Thrombospondins
D006023:Glycoproteins; D019699:Thrombospondins; D013917:Thrombin