Accelerated Publication - Activation of platelet-transforming growth factor beta-1 in the absence of thrombospondin-1

Thrombospondin-1 (TSP-1) has been shown to bind and activate transforming g rowth factor-beta 1 (TGF-beta 1). This observation raises the possibility t hat TSP-1 helps to sequester TGF-beta 1 in platelet alpha granules and acti vates TGF-beta 1 once both proteins are secreted. Herein, we evaluated the level of active and latent TGF-beta 1 in the plasma and in the supernatant of thrombin-treated platelets from TSP-1 null and wild-type mice on two gen etic backgrounds (C57BL/6 and 129Sv). The plasminogen activator inhibitor-1 /luciferase bioassay and an immunological assay were used to determine acti ve and latent TGF-beta 1, No significant differences were observed in the l evels of active and latent TGF-beta 1 in the supernatant of thrombin-treate d platelets from TSP-1 null and wildtype mice. Active and latent TGF-beta 1 were significantly increased in the plasma and platelets of C57BL/6 mice a s compared with 129Sv mice. In addition, there was an increase of plasma le vel of latent TGF-beta 1 in TSP-1 null mice as compared with wild-type mice on the C57BL/6 background but not on the 129Sv background. No active TGF-b eta 1 was observed in the plasma of either TSP-1 null and wild-type mice. T hese data indicate that TSP-I does not function as a chaperon for TGF-beta 1 during platelet production and does not activate significant quantities o f secreted TGF-beta 1 despite a vast excess in the number of TSP-1 molecule s as compared with TGF-beta 1 molecules. Because platelet releasates from T SP-1 null mice contain active TGF-beta 1, we suggest that other important m echanisms of physiological activation of TGF-beta 1 probably exist in plate lets.