IN VIVO INTERACTIONS OF PLATELETS AND LEUKOCYTES WITH THE ENDOTHELIUM IN ANTIGEN-INDUCED ARTHRITIS OF MICE ROLE OF P-SELECTIN

Abstract

Objectives: Platelets are suggested to participate in the pathogenesis of rheumatoid arthritis. We showed for the first time in vivo an increase of platelet-endothelial cell interactions in mice with Antigen-induced-Arthritis (AiA). However, underlying mechanisms are not clear so far. Therefore, the aim of the present study was to investigate first the impact of P-selectin on AiA and second the influence of platelet P-Selectin on the endothelial damage and activation of leukocytes by means of intravital microscopy.

Methods: In the first part C57/Bl6 and P-selectin deficient mice were disposed in four groups (n=7; control/AiA per strain). In the second part ex-vivo labelled platelets were transferred between different strains in AiA. The extent of AiA was assessed by knee joint swelling and by histological scoring. Platelet- and leukocyte-endothelium interactions were investigated.

Results: In arthritic P-selectin deficient mice compared to arthritic C57/Bl6 mice, platelet interaction was significantly reduced and reached the level of both control groups without AiA. In addition interaction of leukocytes in P-selectin deficient arthritic animals was significantly decreased in comparison to arthritic C57/Bl6 animals. Swelling of the knee joint and histological score was reduced in arthritic P-selectin deficient mice compared to arthritic C57/Bl6 mice. In the second part a significant increase of leukocyte-endothelial cell interaction in P-selectin deficient arthritic recipients was shown if P-selectin sufficient platelets were donated. If P-selectin deficient platelets were donated, the number of adherent leukocytes was significantly reduced.

Conclusion: We demonstrated for the first time in vivo a significant decrease of the interaction of platelets and leukocytes with the endothelium in P-selectin deficient mice with AiA and a reduction of clinical and histological symptoms of arthritis. Furthermore we showed that platelets provide storage of P-selectin for the recruitment of leukocytes in P-selectin deficient animals and therefore platelets seem to play a critical role in leukocyte-endothelial cell interaction. These findings suggest that P-Selectin is involved in the development and maintenance of arthritis and it could be at least partly responsible for the leukocyte tissue damage in AiA. Therefore, a reduced presence of P-selectin due to inhibition of platelets could be a new option for treatment of rheumatoid arthritis.