Issekutz A C, Mu J Y, Liu G, Melrose J, Berg E L
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Arthritis Rheum. 2001 Jun;44(6):1428-37. doi: 10.1002/1529-0131(200106)44:6<1428::AID-ART238>3.0.CO;2-U.
To determine the role of the endothelial cell adhesion molecules E- and P-selectin in the development and severity of adjuvant-induced arthritis (AIA) in the rat.
Lewis rats were immunized subcutaneously with Mycobacterium butyricum (Mb), and blocking monoclonal antibodies (mAb) to rat E- and P-selectin were administered. Clinical score, radiolabeled (51Cr and 111In) blood polymorphonuclear leukocyte (PMN) and monocyte migration to joints, and histologic features were monitored.
When mAb treatment was started on day 5 postimmunization with Mb (preclinical stage), development of AIA was significantly (P < 0.01) inhibited by mAb to E- but not to P-selectin (mean score on day 14 control 10.2, anti-E 2.8, anti-P 9.1). This was associated with markedly decreased migration (by 66-94%) of PMN and monocytes to arthritic joints and diminished cartilage degradation. When treatment was delayed until animals showed signs of arthritis (day 10 postimmunization), only a marginal and variable effect was observed as compared with blockade during the preclinical (day 5) stage. E-selectin blockade on day 5 and day 7 postimmunization resulted in inhibition of antigen-dependent T cell-mediated inflammation, since it decreased T cell migration to sites of dermal-delayed hypersensitivity induced by Mb without affecting migration to concanavalin A or cytokines. The proliferative response of T cells to Mb in vitro was not altered.
E-selectin plays an important role early in the development of AIA. This adhesion molecule may contribute to the migration of antigen-reactive T cells to peripheral tissues, including the joints where T cells initiate the arthritis.
确定内皮细胞黏附分子E-选择素和P-选择素在大鼠佐剂性关节炎（AIA）的发生发展及严重程度中的作用。
用丁酸分枝杆菌（Mb）皮下免疫Lewis大鼠，并给予大鼠E-选择素和P-选择素的阻断单克隆抗体（mAb）。监测临床评分、放射性标记（51Cr和111In）的血液多形核白细胞（PMN）和单核细胞向关节的迁移以及组织学特征。
当在免疫Mb后第5天（临床前期）开始mAb治疗时，E-选择素mAb可显著（P<0.01）抑制AIA的发生，而P-选择素mAb则无此作用（第14天的平均评分：对照组为10.2，抗E组为2.8，抗P组为9.1）。这与PMN和单核细胞向关节炎关节的迁移显著减少（减少66%-94%）以及软骨降解减轻有关。当治疗延迟至动物出现关节炎体征时（免疫后第10天），与临床前期（第5天）进行阻断相比，仅观察到轻微且多变的效果。免疫后第5天和第7天进行E-选择素阻断可抑制抗原依赖性T细胞介导的炎症，因为它减少了T细胞向由Mb诱导的皮肤迟发型超敏反应部位的迁移，而不影响其向刀豆蛋白A或细胞因子的迁移。T细胞在体外对Mb的增殖反应未改变。
E-选择素在AIA发生早期起重要作用。这种黏附分子可能有助于抗原反应性T细胞迁移至外周组织，包括T细胞引发关节炎的关节。
