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

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. [ABSTRACT FROM AUTHOR]