Silverstein R L, Nachman R L
J Clin Invest. 1987 Mar;79(3):867-74. doi: 10.1172/JCI112896.
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.
血小板反应蛋白（TSP）是一种多功能血小板糖蛋白，由包括单核细胞和巨噬细胞在内的多种培养细胞合成。我们现在报告，125I-TSP能特异性、饱和性且可逆地与小鼠腹腔巨噬细胞以及单核细胞样人细胞系U937的细胞结合，解离常数为6.7 - 14.5×10⁻⁸M，每个细胞有3 - 4×10⁵个结合位点。TSP介导凝血酶刺激的血小板与U937细胞和人血单核细胞之间的黏附相互作用。使用灵敏的玫瑰花结试验，我们发现静息血小板不会使单核细胞形成玫瑰花结，而凝血酶刺激的血小板能使超过90%的单核细胞形成玫瑰花结。单克隆和多克隆抗TSP抗体以及TSP本身都能显著抑制玫瑰花结的形成。对照抗体、肝素、纤连蛋白、纤维蛋白原以及纤连蛋白黏附四肽Arg-Gly-Asp-Ser均不能抑制玫瑰花结的形成。因此，TSP可能作为一种分子桥梁，在早期血管损伤部位将活化的血小板与单核细胞连接起来。这种相互作用在血栓形成的调节和动脉粥样硬化的起始过程中可能至关重要。
