In vivo assessment of synovial microcirculation and leukocyte-endothelial cell interaction in mouse antigen-induced arthritis

Objective: The microcirculation and leukocyte-endothelial cell interaction in synovial tissue of an inflamed joint are known to play a crucial role in the pathogenesis of rheumatoid arthritis The aim of this study was to char acterize the in vivo changes in the microvasculature and in leukocyte-endot helial cell interactions in the mouse synovial tissue using intravital fluo rescence microscopy in three stages of antigen-induced arthritis. The expre ssion of E- and P-selectin and ICAM-1 a ere also studied using immunohistoc hemistry. Methods: Antigen-induced arthritis (AiA) was produced in Balb/c mice. The s everity of arthritis at three different phases was quantified using a clini cal and histological score. For the intravital fluorescence microscopy meas urements, the patella tendon was partially resected for visualization of th e intraarticular synovial tissue of the knee joint. The number of rolling a nd adherent leukocytes, functional capillary density (FCD) and RBC velocity were quantitatively measured in synovial microvessels. Expression of ICAM- 1, E- and P-selectin was assessed by immunohistochemistry. Results: There was a significant increase in the leukocyte rolling fraction in postcapillary; venules in the acute phase of AiA (from 0.26 +/- 0.05 in controls to 0.45 +/- 0.04 8 d after AiA induction). The number of leukocyt es adherent to the endothelium Tvas significantly elevated in all phases of arthritis (from 121 +/- 27 in controls to 376 +/- 62 mm(2) 63 d after AiA- induction). Functional capillary density was significantly enhanced in the acute (332 +/- 15 cm/cm(2)) and intermediate phases (320 +/- 15 cm/cm(2)) c ompared to control values (227 +/- 15 cm/cm(2)). Arthritis resulted in a di stinct increase in the expression of ICAM-1 on the synovial endothelium in all phases of AiA. E- and P-selectin expression were detected only in the a cute phase. Conclusion: Our model provides new insights into the microcirculatory chang es which occur in the synovial tissue of an arthritic joint.