Electrical charge of the antigen determines its localization in the mouse knee joint. Deep penetration of cationic BSA in hyaline articular cartilage

Abstract

Intraarticular injection of cationic bovine serum albumin (BSA) induces a chronic arthritis in immunized mice, whereas the negatively charged native BSA fails to cause a protracted joint inflammation. In this study the authors examined the role of antigenic charge as a determinant of antigen retention and exact localization within the knee joint. Immune and nonimmune mice received an intraarticular injection of either radiolabeled native BSA (125I-BSA) or charge-modified BSA rendered cationic by amidation (aBSA), and autoradiographs were prepared of whole joint sections at various days after injection. As has been shown in the rabbit, the retention of the negatively charged native BSA is largely dependent upon the presence of antibodies. In nonimmune mice the radiolabeled antigen was hardly detectable after Day 1. In immune mice antibody-mediated retention of BSA was found in the ligaments and fibrous cartilage structures of the joint but appeared to be absent at the hyaline cartilage. In contrast, large amounts of the cationic aBSA were retained at all collagenous structures of the joint, the most striking observation being the deep penetration in the dense hyaline cartilage. This was found both in immune and nonimmune mice, which indicates that the deep penetration was not due to cartilage damage occurring under inflammatory conditions. With different dosages of aBSA it was found that the presence of antibodies may modulate the retention pattern in immune mice. Deep diffuse penetration into the dense hyaline cartilage, together with some surface labeling, was observed after injection of a high dose (60 micrograms), whereas mere surface labeling was found with the low dose (6 micrograms). Distinct superficial labeling was not seen in nonimmune mice, which suggests that this pattern represents immune complex formation at the cartilage surface. Immunofluorescence studies on undecalcified whole joint sections confirmed the deep penetration of the cationic antigen and supported the presence of immune complexes at the cartilage surface, because intense complement and Ig staining was detectable at this site. Our data indicate that antigenic charge determines the antigen retention in the joint both quantitatively and qualitatively. Negatively charged native BSA has no affinity for cartilage, high amounts of antibodies are needed for its retention in the joint, retention by this immune complex formation is largely restricted to the loose collagenous tissues, and the capacity to retain anionic antigen in the joint is therefore low.(ABSTRACT TRUNCATED AT 400 WORDS)