In vivo interactions of platelets and leucocytes with the endothelium in murine antigen‐induced arthritis: the role of P‐selectin

Abstract

Objective: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet–endothelial cell interactions in mice with antigen‐induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P‐selectin in AiA by means of intravital fluorescence microscopy (IVM).Methods: C57/Bl6 mice and P‐selectin‐deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence‐labelled platelets and leucocytes were investigated by IVM.Results: In arthritic P‐selectin‐deficient mice (rolling: 0.05±0.01; adherent: 130±20 mm−2), compared to arthritic C57/Bl6 mice (rolling: 0.20±0.04; adherent: 1910±200 mm−2), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P‐selectin‐deficient arthritic animals (rolling: 0.12±0.06; adherent: 387±37 mm−2) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21±0.06; adherent: 1492±284 mm−2; p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P‐selectin‐deficient mice compared to arthritic C57/Bl6 mice.Conclusion: We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P‐selectin‐deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte–endothelial cell interactions depend at least partially on platelet P‐selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.