Enhanced leukocyte endothelial cell interaction in iNOS-deficient mice with antigen-induced arthritis

Background/aim: Nitric oxide production by the inducible NO synthase in the synovium and chondrocytes is known to be enhanced during chronic joint inf lammation and aseptic loosening of joint prostheses. Beneficial effects of iNOS inhibition in experiment arthritis have been suggested. However, in en dotoxemia of iNOS-deficient mice increased leukocyte adhesion and emigratio n were found. The aim of our study was to analyze the synovial microcircula tion and leukocyte endothelial cell interactions in iNOS-deficient mice wit h antigen-induced arthritis (AiA) in vivo. Methods: 14 homocygote iNOS-deficient (iNOS KO C57BL6/J x 129SvEv; Merck & Co., Rahway, NJ, USA) and 14 iNOS-positive (C57BL6/J x 129SvEv) mice were u sed for our study. The patella tendon was cut transversally, which allows f or visualization of the intra articular synovial tissue of the knee joint u sing intravital fluorescence microscopy. Animals were allocated into four g roups (iNOS +/+, iNOS +/+ with AiA, iNOS -/- and iNOS -/- with AiA) (n = 7 each group). On day 8 after arthritis induction (acute phase), functional c apillary density as well as the fraction of rolling leukocytes and the numb er of adherent leukocytes were quantitatively analyzed in synovial postcapi llary venules. Results: Functional capillary density or leukocyte-endothelial cell interac tion were not altered in healthy iNOS-deficient mice in comparison to iNOS +/+ animals. However, in iNOS-deficient animals with AiA there was a signif icant increase in the fraction of rolling (0.51 +/- 0.05) and in the number of adherent leukocytes (729 +/- 126 mm(-2)) in comparison to wild type mic e with AiA (0.33 +/- 0.07 and 565 +/- 110 mm-2) (MW +/- SEM, p < 0.05). Conclusion: In our study, there was an enhanced leukocyte accumulation in i NOS-deficient mice with antigen-induced arthritis in comparison to iNOS-pos itive animals with arthritis. Thus, NO production by iNOS can be regarded a s a protective response in reducing leukocyte adhesion in antigen-induced a rthritis.