Summary
Moderate consumption of alcoholic beverages is associated with a reduction in thromboembolic
complications of coronary artery disease, possibly partially attributable to inhibition
by ethanol of platelet responses to some aggregating agents. Although ethanol is known
to inhibit thrombin-induced secretion of platelet dense granule contents, the effect
of ethanol on secretion of α-granule and lysosomal contents has not been studied.
Using suspensions of washed platelets, and a range of thrombin concentrations (up
to 0.1 U/ml), we examined the effect of 87 mM ethanol on secretion of [14C]serotonin from prelabelled platelets as a measure of secretion of dense granule
contents. Secretion of α-granule and lysosomal contents was examined by flow cyto-metric
measurement of the surface expression of CD62P (P-selectin) and CD63, respectively.
Secretion of the lysosomal enzyme, β-N-acetylglucosaminidase was also quantified.
Results were expressed as % of maximum response induced by 1 U/ml thrombin. Ethanol
inhibited the thrombin-induced secretion of both dense and α-granule contents (P <0.001,
2-way ANOVA), and of lysosomal contents (P <0.005 for CD63 expression and P <0.001
for β-N-acetylglucosaminidase secretion). When platelets were pretreated with aspirin,
thrombin-induced secretion of storage granule and lysosomal contents was slightly
inhibited, but secretion was inhibited by ethanol to the same extent as the untreated
platelets, indicating that this inhibition was independent of thromboxane A2. Surface expression of CD63 occurred at lower thrombin concentrations than those
required for secretion of β-N-acetylglucosaminidase, possibly due to the presence
of some CD63 on granule membranes. Although the role of lysosomal contents in thrombus
formation is not established, some constituents of storage granules are known to augment
thrombus formation; ethanol’s inhibition of their secretion by stimulated platelets
may contribute to its beneficial effect on thromboembolism.
Presented in part at the XVIth Congress of the International Society on Thrombosis and Haemostasis, Florence, Italy,
June 1997.
