Thrombospondin (TSP, glycoprotein G, thrombin-sen-sitive protein) is a large glycoprotein (450 kD) first described in 1971 by Baenziger et al. 1'2 as a secretion product of thrombin-stimulated human platelets. 1" 4 It is found in the alpha granules of resting platelets56 and makes up approximately 2% to 4% of total platelet protein78 and 20% to 30% of released protein. 2 Subsequent work in several laboratories9" 11 has revealed that TSP is made up of three probably identical, disutfide-linked monomers organized into a multinodular configuration. A model of the multidomain TSP molecule is shown in Figure 1. The native three-dimensional structure of TSP is calciumdependent, 12" 14 as reflected in an increased susceptibility of the protein to proteolysis in the presence of calcium chelators. Thrombospondin does not circulate in appreciable concentrations (~ 20 ng/ml); 78'15 however, the tissue distribution is broad. Jaffe and collaborators have found that fibroblasts, 16 endothelial cells, 17 and monocytes18 in culture produce TSP. McPherson et at. 19 also identified TSP in endothelial cells, while Raugi et al. 20 have shown that TSP is produced by aortic smooth muscle cells and fibroblasts. Sage et al. 21 have shown TSP production by Type II alveolar pneumocytes.

TSP may be an important constituent of extracellular matrices (ECM). It has been found by immunofluorescent techniques22 in vessel wall, basement membrane, and glandular connective tissue of fixed human tissues. Fibroblasts, endothelial cells, and aortic smooth muscle cells in culture16'1823 incorporate TSP into the ECM. The presence of TSP in the matrix appears to be under cell-cycle regulatory control. 2425 Proliferating mesenchymal cells synthesize significantly more TSP than non-growing cells and platelet-derived growth factor (PDGF) induces TSP