Platelet-Derived Growth Factor Production During the Platelet Release Reaction Independent of The Endoperoxide Pathway.

Ross et al (P.N.A.S. 71:1207, 1974) showed that a platelet-derived growth factor (PGF) promotes the proliferation of arterial smooth muscle cells (SMC) and thus may be important in atherogenesis. Although PGF is found in plasma when platelets are exposed to thrombin or collagen it has not been conclusively established that the material is released from platelet granules. Inhibitors of the release reaction and of platelet cyclo-oxygenase were used to examine the relation between release of 14C-serotonin (14C-5HT) from rabbit platelets and the appearance of PGF in the suspending fluid. Washed platelets (2 × 106/mm3) were suspended in Tyrode solution containing albumin and apyrase at 37°C and treated with collagen suspension, thrombin or ADP. After 5 min. the platelets were removed and the supernate assayed for 14C-5HT, malondialdehyde (MDA) and PGF. Incorporation of 3H-thymidine into cultured rabbit aorta SMC DNA was used as an index of PGF concentration. There was a direct relation between the concentration of collagen or thrombin and the amount of PGF in the supernate. Indomethacin (20μM) or sulfinpyrazone (ImM) reduced 14C-5HT release in response to collagen from 45-65% to 5-8%, completely blocked MDA formation and reduced the amount of PGF in the supernate to 33-44% of control values. These inhirbitors reduced release caused by thrombin (5U/ml) from 90-95% to 85-88% and, although they completely blocked MDA formation, did not decrease PGF. PGF was not made available by aggregation of platelets with ADP.(Release does not occur with rabbit platelets exposed to ADP). Thus, the appearance of PGF does not depend on primary aggregation but is associated with the release reaction and is independent of the endoperoxide pathway.