MORPHOLOGIC AND ULTRASTRUCTURAL EVIDENCE FOR INTERLEUKIN-6 INDUCED PLATELET ACTIVATION

The in vitro effect of IL-6 on platelet activation was investigated. W hen human platelets were incubated with high (1,000 ng/ml) or low (1 n g/ml) dose IL-6, expression of GMP-140 was enhanced by 42% (N = 6; P < 0.009) and 46% (N = 6; P < 0.061) in 1 hr low and high dose IL-6-plat elet incubations, respectively, as assessed by flow cytometry. In plat elet specimens incubated with high dose IL-6 for 3 hr, a 70% (N = 6; P < 0.009) increase in GMP-140 expression over control was observed. Pa rallel high dose IL-6 incubations subjected to scanning electron micro scopic studies revealed a 3.4-fold increase (N = 6; P < 0.001) in sphe roid morphologic platelet forms in 1 hr incubations in comparison to c ontrol platelet preparations, whereas in 3 hr IL-6-platelet incubation s, a 96% increase in dendritic platelet forms was observed (N = 6; P < 0.001). Significant increases in platelet ATP levels were observed in both 1 min and 1 hr high dose and low dose IL-6 platelet incubations. In 3 hr high dose-IL-6 platelet incubations, a significant 18% (N = 8 ; P < 0.001) decrease in platelet ATP was parallelled by a significant 40% increase (N = 8; p < 0.014) in plasma ATP in the same specimens. This increased plasma ATP was highly correlated with a reduction in pl atelet ATP when analyzed by bivariate regression analysis. Lastly, tra nsmission electron microscopic analysis demonstrated a significant red uction in dense granule number and ratio of dense granule surface area /cell surface area in 3 hr high dose IL-6 incubations. These findings suggests that IL-6 activates platelets in vitro. (C) 1995 Wiley-Liss, Inc.