Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice

Abstract

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.