title: Deletion of mPGES-1 affects platelet functions in mice.
abstract: Microsomal prostaglandin E2synthase-1 (mPGES-1) constitutes an essential player in inflammation and is involved in the pathogenesis of rheumatoid arthritis. Platelets participate in the regulation of inflammatory processes by the release of proinflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE2pathway in platelet functions has not been investigated. In the present study we report a significant impact of mPGES-1 on platelet functions during inflammation. Wild-type (WT) and mPGES-1-/-knockout (KO) mice were stimulated with lipopolysaccharide (LPS) for 24 h. Platelet counts and activation were assessed by flow cytometry analysing CD62P-CD154 expression, PMP numbers, platelet-leukocyte aggregates and platelet aggregation. The accumulation of platelets and fibrinogen in the liver was analysed 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 was significantly decreased in WT, but not in KO mice. Platelet activation, platelet-leukocyte aggregates and PMP numbers were all significantly lower in KO mice compared with WT mice after LPS treatment. In addition, KO mice displayed a significant reduction in platelet aggregationex vivoIn 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 was significantly lower compared with the WT one. Our results demonstrate that systemic inhibition of mPGES-1 prevents platelet activation, which should have important implications with regard to the cardiovascular safety of mPGES-1 inhibitors.
authors.affiliation: Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Unit of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Joan
authors.initials: J
authors.lastname: Raouf
authors.affiliation: Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Unit of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mobarrez
authors.affiliation: Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Unit of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.affiliation: Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Unit of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Per-Johan
authors.initials: PJ
authors.lastname: Jakobsson
authors.affiliation: Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Unit of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden marina.korotkova@ki.se.
authors.forename: Marina
authors.initials: M
authors.lastname: Korotkova
keywords: mPGES-1; platelet-derived microparticles; platelets