The mechanism of trapping of immune complexes in experimental antigen-induced arthritis

Abstract

The role of acute inflammation and of specific antibody in the retention of antigen in joint collagenous tissues of immunized rabbits was examined. The role of the acute synovitis occurring immediately after IA antigen injection in the retention of immune complexes was investigated by the concomitant IA injection of trace amounts of 1258-BSA and mono-sodium urate crystals and by the production of an acute Arthus reaction using an unrelated antigen in doubly immunized rabbits. In neither case was more 125I-BSA retained in the inflamed joint tissues compared to the contralateral noninflamed joints 7 days after antigen injection. In addition, immunized rabbits depleted of ciruclating polymorphonuclear leukocytes by previous treatment with nitrogen mustard retained 2.7 times more antigen than control, nonimmune animals. In another experiment, antigen retention in joint collagenous tissues was greatest 30 min after IA injection, before the appearance of acute inflammatory synovitis. These findings suggest that acute inflammation is not a major factor in the retention of antigen in collagenous tissues. To investigate the role of antibody in the retention of antigen, nonimmune rabbits were injected i.v. with purified anti-BSA antibody three days prior to the intraarticular injection of BSA. Over 20 times more antigen was retained irreversibly in collagenous tissues obtained from the injected joints of passively immunized animals as compared to similar tissues of control rabbits. When rabbits were injected i.v. with purified anti-BSA antibody and either killed 20 min or 3 days later, in vitro binding of antigen by joint collagenous tissues was seen only in animals where antibody was allowed to equilibrate with the extravascular space for 3 days. These findings indicate that retention of antigen depends on the presence of extravascular antibody. It is concluded that the trapping of immune complexes in collagenous joint tissues of immunized animals depends on: (1) the presence of antibody in the extravascular space; (2) the diffusion of antigen or soluble complexes into this space; (3) the interaction of antigen or soluble complexes with extravascular antibody with subsequent formation of larger and more insoluble complexes, and (4) the trapping of these complexes in the collagen fiber meshwork.