Taylor P C, Chu C Q, Plater-Zyberk C, Maini R N
Kennedy Institute of Rheumatology, London, UK.
Immunology. 1996 Jun;88(2):315-21. doi: 10.1111/j.1365-2567.1996.tb00021.x.
Collagen-induced arthritis in susceptible mice is widely accepted as an experimental model for human rheumatoid arthritis (RA). We have investigated the role of the Mac-1 integrin beta 2 in the development and maintenance of arthritis by means of in vivo administration of 5C6 monoclonal antibody (mAb) to block this receptor. Injection of a single dose of 5C6 mAb (0.5 mg, intraperitoneally) prior to the expected onset of collagen-induced arthritis in DBA/1 mice diminished the severity of subsequent disease in these animals, as assessed both clinically and histologically (P < 0.01, chi 2). In the DBA/1 to severe combined immunodeficiency (SCID) transfer model of arthritis, the incidence of clinical arthritis was significantly reduced in SCID mice receiving maintained 5C6 treatment commencing the day prior to administration of donor splenocytes. Histological evaluation of joints from animals without clinically evident arthritis confirmed the absence of an inflammatory infiltrate in 22/27 joints examined. In a minority of these joints, however, synovial hyperplasia was apparent. In contrast, delaying antibody administration until 10 days after donor spleen cell transfer failed to protect three of five SCID recipients. These results confirm a functional role for Mac-1 in the generation of collagen-induced arthritis in mice. Since mAb 5C6 is non-cytotoxic, its action must be by blockade of the interactions between Mac-1 and its natural ligand(s). Our findings support the hypothesis that cells expressing Mac-1 play an important role in the induction and maintenance of joint damage in collagen-induced arthritis.
在易患关节炎的小鼠中，胶原诱导性关节炎被广泛认为是人类类风湿关节炎（RA）的实验模型。我们通过体内注射5C6单克隆抗体（mAb）阻断该受体，研究了Mac-1整合素β2在关节炎发生和维持过程中的作用。在DBA/1小鼠预期发生胶原诱导性关节炎之前，腹腔注射单剂量的5C6 mAb（0.5 mg），临床和组织学评估均显示，这减轻了这些动物随后疾病的严重程度（P < 0.01，卡方检验）。在DBA/1到严重联合免疫缺陷（SCID）的关节炎转移模型中，从供体脾细胞给药前一天开始接受持续5C6治疗的SCID小鼠，临床关节炎的发生率显著降低。对无临床明显关节炎动物的关节进行组织学评估证实，在检查的27个关节中有22个没有炎性浸润。然而，在少数这些关节中，滑膜增生明显。相比之下，将抗体给药推迟到供体脾细胞转移后10天，未能保护5只SCID受体中的3只。这些结果证实了Mac-1在小鼠胶原诱导性关节炎发生过程中的功能作用。由于mAb 5C6无细胞毒性，其作用必定是通过阻断Mac-1与其天然配体之间的相互作用。我们的研究结果支持这样的假设，即表达Mac-1的细胞在胶原诱导性关节炎的关节损伤诱导和维持中起重要作用。
