Abstract
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.