PLATELETS FROM ECLAMPSIA PATIENTS HAVE REDUCED MEMBRANE MICROVISCOSITY AND LOWER ACTIVITIES OF THE SIGNALING ENZYMES

It has been shown that platelets from patients suffering from eclampsi a are hyporesponsive to stimulation by agonists like thrombin and ADP. Although platelet hyporeactivity contributes to the pathogenesis of t he disease process, the cause for this is still not known. Platelet ag gregation and secretion are membrane-based phenomena initiated by the processes of cell signalling. Hence. to understand the mechanisms unde rlying platelet hyporeactivity in eclampsia, membrane microviscosity a nd activities of the signalling enzymes Mere measured in human platele ts stimulated with thrombin. Membrane fluidity was determined from the steady-state fluorescence anisotropy of diphenylhexatriene incorporat ed in cell membranes. Activities of phospholipase C and protein kinase C in stimulated platelets were assessed from the extents of phosphati dic acid generation and pleckstrin phosphorylation, respectively. Plat elet membrane microviscosity in eclampsia (2.3 +/- 0.2 SEM, n = 5) was significantly lower (P < 0.05) than that in the matched gravid contro l subjects (3.1 +/- 0.2, n = 4). In eclampsia, generation of phosphati dic acid and phosphorylation of pleckstrin were decreased by 25%, (P < 0.05:, n = 3) and 35% (P < 0.05, n = 3), respectively, after 60 sec o f platelet stimulation. It was concluded that the hyporeactive platele ts obtained from eclampsia have more fluid membranes and diminished ac tivities of phospholipase C and protein kinase C. In summary, this stu dy shows that alterations in membrane fluidity and activities of the s ignalling enzymes (phospholipase C and protein kinase C) may contribut e to the diminished platelet responsiveness observed in the eclamptic condition. (C) 1998 Elsevier Science Ltd. All rights reserved.