We studied the influence of antigenic charge on the handling of intraarticular
antigen by the joint and on the ability of the
antigen to induce chronic
arthritis. Three different
antigens were used: anionic native
bovine serum albumin (BSA), and charge modified BSA made cationic (pI 8.5) either by methylation (
mBSA), or amidation (aBSA). 125I-labeled
antigen was injected into the knee joints of nonimmune mice and of mice immunized with
antigen in Freund's complete adjuvant. Intraarticular
antigen retention of the cationic
antigens mBSA and aBSA was significantly increased compared with native BSA, both in immune and non-immune mice. In vitro studies indicated the electrostatic character of the binding of the cationic
antigens to joint tissues and confirmed the large difference in
antigen retention of the
antigens found in vivo. A 100-fold amount of cationic
antigen could be bound to non-cartilaginous collagenous tissue of the joint compared with antibody-mediated trapping of native BSA, and for hyaline articular cartilage, this difference was even greater. In immunized mice, chronic
arthritis only developed after
intraarticular injection of the cationic
antigens. This phenomenon was apparently related to increased retention of
mBSA and aBSA compared with BSA, since
delayed hypersensitivity and humoral immunity were comparable for the three
antigens used. Our data indicate that antigenic charge is an important determinant of
antigen handling by the joint and, in addition, support the concept that the development of chronic
arthritis depends on the amount of
antigen retained in the joint.