Deficiency of leukocyte NADPH oxidase increases joint inflammation in serum-induced arthritis model (44.27)

Abstract

Abstract To elucidate the role of reactive oxygen species (ROS) in modulating tissue inflammation, we established an arthritis model by intraperitoneally injecting the K/BxN serum into wild type and ncf1-/- CGD mice, which have deficiency in p47phox of NOX2. By comparing the joint inflammation index ankle thickening, we found that the serum-induced arthritis were more severe in CGD mice than in wild type mice (30.2 mm ± 4.6 vs. 19.6 mm ± 0.19 on the day 10). These data suggested that lack of leukocyte-produced ROS interferes with the control of the neutrophil-dominant joint inflammation. By depleting neutrophils with anti-Ly6G antibodies, we found that serum-induced arthritis was abrogated in both ncf1-/- and wild type mice, which confirms previous reports that neutrophils play an important role in the induction and progression of serum-induced arthritis. However, the joint reaction in serum-induced diseased ncf1-/- mice, different from wild type mice, could not be reversed by depleting neutrophils. We further analyzed the proinflammatory cytokines, chemokines, and neutrophil-related proteases in ncf1-/- mice and wild type. We also analyzed the redox modulation status of redox response proteins to elucidate the possible mechanisms involved in ROS-mediated innate immunity in regulating the joint inflammation. These data suggest that ROS play an important role in modulating immune system and controlling the tissue inflammation in joints.