Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells.

Abstract

SUMMARY Platelets contain a growth-promoting factor for arterial smooth muscle cells (SMC) that may play a major role in atberogenesis. We have studied some of the effects of the platelet-derived growth factor (PDGF) on human arterial SMC in culture and the release of PDGF from human platelets in relationship to other released substances. Material released from platelets was highly potent in stimulating human SMC to proliferate. A substantial portion of the growth-promoting activity of human serum could be attributed to a factor(s) released from platelets. Similar dose-response patterns to PDGF were observed with human SMC and with mouse 3T3 cells. The time-course of release of PDGF and its concentration dependence on human thrombin were determined in comparison with serotonin, ADP, ATP, an acid bydrolase, platelet factor 4 (PF4), and /3-thromboglobulln (/JTG). PDGF activity was assayed by stimulation of the incorporation of 'H-thymidine into DNA of 3T3 cells; PF4 and /JTG were measured by newly developed radioimmunoassays. PDGF, PF4, and /JTG were released from platelets by lower concentrations of thrombin than those required for release of the other components. The results suggest that PDGF, PF4, and /3TG are localized in the platelet in granules different from either the dense bodies (that contain serotonin, ADP, ATP) or the acid hydrolase-containing granules, possibly in a-granules. The contents of these PDGFcontainlng a-granules are actively released during the release reaction and are particularly sensitive to release by low doses of thrombin.