Background
In rheumatoid arthritis (RA), constitutive activation of integrins promotes retention of oxidatively stressed, activated T lymphocytes in synovial tissue where they perpetuate inflammation through cell–cell contact with synovial stromal cells, macrophages and plasma cells. We have previously demonstrated that activation of Ras GTPases, coupled with inactivation of the related GTPase Rap1, is responsible for oxidative stress in RA synovial fluid (SF) T lymphocytes [1]. Inactivation of Rap1, however, is incongruous with the observation that Rap1 signaling is absolutely required for integrin function in T lymphocytes. Because T lymphocytes express multiple Ras homologs (H-Ras, K-Ras, and N-Ras), we explored the possibility that these proteins may make distinct contributions to reactive oxygen species (ROS) regulation and integrin function in T lymphocytes.