ADP And Epinephrine-Induced Release Of Platelet Fibrinogen

Abstract

Added fibrinogen is said to be essential for induction of platelet aggregation and release by ADP and epinephrine. Furthermore, both ADP and epinephrine induce binding of fibrinogen to the platelet surface. In the present study gel-filtered human platelets were examined to determine whether they would aggregate and release platelet fibrinogen in response to ADP or epinephrine without exogenous fibrinogen. Platelets gel-filtered into Tyrode’s buffer containing ImM Mg++, no added Ca++, and 0.35% bovine serum albumin had a fibrinogen concentration in the supernatant of less than 1 nM. After aggregation by ADP or epinephrine the fibrinogen concentration in the supernatant ranged from 11 to 41 nM. ADP and epinephrine each induced biphasic aggregation and release of platelet factor 4 and β-thromboglobulin as well as of fibrinogen. Protein release by epinephrine was coincidental with dense granule adenine nucleotide release. Because Ca++ ions affect fibrinogen binding to platelets, the effect of Ca++ on aggregation and protein release was examined and it was found that both were inhibited by added Ca++ at 1-2 mM. The ability of gel-filtered platelets to undergo ADP and epinephrine induced aggregation and release in the absence of exogenous fibrinogen suggests that released platelet fibrinogen can support these processes. The concentrations of released fibrinogen in these experiments were lower than those reported to be necessary for exogenous fibrinogen for support of aggregation, suggesting that released fibrinogen may interact more efficiently with the platelet membrane. The amount of released fibrinogen in these experiments is similar to the Kd for high-affinity fibrinogen binding reported by Niewiarowski et al. (30nM). Finally, although inhibition of ADP and epinephrine induced aggregation and release by physiologic Ca++ concentrations implies that these processes do not occur in vivo, it is likely that platelet fibrinogen released by collagen or thrombin does function physiologically.