Studies on the effect of rat C-reactive protein on platelet aggregation and secretion

Randell, Edward (1992) Studies on the effect of rat C-reactive protein on platelet aggregation and secretion. Doctoral (PhD) thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (17MB)

Abstract

Rat C-reactive protein (CRP) is a member of a family of proteins, collectively termed C-reactive proteins, present in a variety of species, from simple invertebrates to humans. In this thesis, the effect of rat CRP on platelet function was examined. Rat CRP inhibited, in a dose-dependent manner, platelet aggregation and serotonin secretion using either ADP or thrombin as agonist. Inhibition of platelet aggregation induced by these agonists required the binding of rat CRP to platelets. This binding was specific, saturable, of high affinity and calcium-sensitive. The rat [¹²⁵I]CRP bound to platelets was displaced by either unlabelled rat CRP or phosphorylcholine. This binding was also inhibited by either rabbit CRP or phosphorylcholine. -- Rat CRP inhibited platelet activating factor (PAF)-induced platelet aggregation. Results showed that the inhibition of PAP-induced platelet aggregation required the binding of rat CRP either to platelets or to PAF. -- Platelet functional responses are mediated by the participation of platelet phospholipases in signal transduction pathways. Therefore the effect of rat CRP on agonist-induced platelet phospholipase activity was examined. The results confirmed the presence of phosphatidylcholine-specific phospholipase C (PC-PLC) in rat platelets. This platelet PC-PLC was inhibited by rat CRP in a dose-dependent manner. In contrast, rat CRP did not inhibit either phospholipase A₂ or phosphatidylinositol-specific phospholipase C activity. It was, therefore, concluded that if the formation of phosphatidylcholine-derived diacylglycerol (DAG) by PC-PLC is involved in the regulation of platelet functional response, then the inhibition of DAG formation by rat CRP may be critical in the observed inhibition of platelet aggregation and serotonin secretion by rat CRP.

Actions (login required)

View Item