Ruth Jeffrey H, Amin M Asif, Woods James M, He Xiaodong, Samuel Sharon, Yi Nengjun, Haas Christian S, Koch Alisa E, Bullard Daniel C
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Arthritis Res Ther. 2005;7(5):R959-70. doi: 10.1186/ar1770. Epub 2005 Jun 15.
The selectins, along with very late antigen-4 and CD44, have been implicated in mediating leukocyte rolling interactions that lead to joint recruitment and inflammation during the pathogenesis of rheumatoid arthritis. Previously, we showed that P-selectin deficiency in mice resulted in accelerated onset of joint inflammation in the murine collagen-immunized arthritis model. Here, we report that mice deficient either in E-selectin or in E-selectin and P-selectin (E/P-selectin mutant) also exhibit accelerated development of arthritis compared with wild type mice in the CIA model, suggesting that these adhesion molecules perform overlapping functions in regulating joint disease. Analyses of cytokine and chemokine expression in joint tissue from E/P-selectin mutant mice before the onset of joint swelling revealed significantly higher joint levels of macrophage inflammatory protein-1alpha and IL-1beta compared to wild-type mice. IL-1beta remained significantly increased in E/P-selectin mutant joint tissue during the early and chronic phases of arthritis. Overall, these data illustrate the novel finding that E-selectin and P-selectin expression can significantly influence cytokine and chemokine production in joint tissue, and suggest that these adhesion molecules play important regulatory roles in the development of arthritis in E/P-selectin mutant mice.
选择素与极迟抗原-4和CD44一起，参与介导白细胞滚动相互作用，这种相互作用在类风湿性关节炎发病过程中导致关节募集和炎症。此前，我们发现小鼠缺乏P-选择素会导致在小鼠胶原免疫性关节炎模型中关节炎症发病加速。在此，我们报告，在胶原诱导的关节炎（CIA）模型中，缺乏E-选择素或同时缺乏E-选择素和P-选择素（E/P-选择素突变体）的小鼠与野生型小鼠相比，也表现出关节炎的加速发展，这表明这些黏附分子在调节关节疾病中发挥重叠功能。对E/P-选择素突变体小鼠关节肿胀发作前关节组织中细胞因子和趋化因子表达的分析显示，与野生型小鼠相比，巨噬细胞炎性蛋白-1α和IL-1β的关节水平显著更高。在关节炎的早期和慢性阶段，E/P-选择素突变体关节组织中的IL-1β仍显著升高。总体而言，这些数据表明了一个新发现，即E-选择素和P-选择素的表达可显著影响关节组织中细胞因子和趋化因子的产生，并表明这些黏附分子在E/P-选择素突变体小鼠关节炎的发展中发挥重要的调节作用。
