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A2.1 The effect of mPGES-1 deletion on platelet function in mice
  1. J Raouf,
  2. F Mobarrez,
  3. K Larsson,
  4. PJ Jakobsson,
  5. M Korotkova
  1. Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet S-171 76, Stockholm, Sweden

Abstract

Background Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible terminal synthase that generates PGE2 and is one of the key players in inflammation. Genetic deletion and pharmacological inhibition of mPGES-1 are protective in experimental models of inflammation. Platelets play essential roles in homeostasis and modulation of inflammatory processes, activated platelets have been recognised as major players in autoimmune diseases such as rheumatoid arthritis. Targeting mPGES-1 alters eicosanoid profiles and may potentially regulate functions of platelets that are known to express prostanoid receptors.

Objective To investigate the effect of mPGES-1 deletion on platelet function in mice stimulated with LPS.

Methods Wild type (WT) and mPGES -/- (KO) mice (DBA/1lacJ) were injected with 2 μg LPS (n = 6) or saline (n = 5) i.p, for 24 h. Mice were anesthetised and blood was slowly drawn by a syringe containing 100 μl 3.8% sodium citrate and transferred to tubes containing citrate to avoid platelet activation. Platelets were stained with CD41-PE together with CD62-FITC (P-selectin) or CD154-FITC (CD40L) and analysed by whole blood flow cytometry. Platelet activation and platelet-leucocyte interaction was also investigated after ADP stimulation (10 μM).

Results Platelet counts decreased after LPS stimulation in WT mice. P-selectin expression was higher in LPS-induced WT compared with KO mice. CD40L expression was higher after LPS stimulation for both WT and KO mice. The platelet-leukocyte interaction seems to be lower in KO mice. There were no differences in platelet activation after ADP stimulation between WT and KO mice.

Conclusions mPGES-1 deletion affected platelet counts and activation in LPS stimulated mice. The data suggest possible role of mPGES-1 in platelet function during inflammation.

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