mPGES-1 deletion affects platelet functions in mice

Microsomal prostaglandin E2 synthase-1 (mPGES-1) constitutes an essential player of inflammation and is involved in the pathogenesis of rheumatoid arthritis (RA). Platelets participate in the regulation of inflammatory processes by the release of pro-inflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE2 pathway on platelet functions has not been investigated. Here we report a significant impact of mPGES-1 on platelet functions during inflammation. Wild-type (WT) and mPGES-1-/- (KO) mice were stimulated with lipopolysaccharide (LPS) for 24 hours. Platelet counts and activation were assessed by flow cytometry analyzing CD62P - CD154 expression, PMPs number, platelet-leukocyte aggregates and platelet aggregation. The accumulation of platelets and fibrinogen in the liver was analyzed by immunofluorescent staining. In native platelets from WT and mPGES-1 KO mice, there were no differences among the investigated functions. After LPS treatment, the number of platelets were significantly decreased in WT mice, but not in KO. Platelet activation, platelet-leukocyte aggregates, and PMP numbers were all significantly lower in KO mice compared to WT after LPS-treatment. In addition, KO mice displayed a significant reduction in platelet aggregation ex vivo . In the liver of LPS-stimulated WT and KO mice, there were no differences in platelet accumulation, although, the percentage of total vessel area in the KO liver wa...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research