Biomedical subjects
K Morgan
Publications and source records attributed to K Morgan.
Collagen-induced arthritis: antibody production by lymphocytes in vitro.
The in vitro production of anti-bovine type II collagen antibodies by lymphocytes from rats immunised with native bovine type II collagen and adjuvant was measured using a solid-phase enzyme-linked immunoassay. Antibodies to native bovine type II collagen could be detected in culture supernatants from the lymphocytes of rats only if they had been immunised with native bovine type II collagen, but not if immunised with native type I collagen, with keyhole limpet haemocyanin, with buffer or if un-immunised. The antibodies produced also bound to native rat, human and chick type II collagens, to native bovine 1 alpha 2 alpha 3 alpha collagen but not to native type I collagen. The amount of antibody in the cultures was altered by the presence of serum from type II collagen immunised rats or by the presence of either cyclohexamide, colchicine, Concanavalin A, catalase or lipopolysaccharide. Pre-treatment of the lymphocytes with mitomycin-C reduced the amount of anti-collagen antibody. This system can be used to investigate mechanisms controlling anti-collagen antibody production.
Collagen-induced arthritis--use of the direct and indirect haemolytic plaque-assay to study the humoral response to collagen.
Using both the direct and indirect haemolytic plaque assay, lymphocytes secreting antibodies to native type II collagen could be detected in the lymph nodes, spleen and blood of collagen-immunised rats. Sprague-Dawley, but not Alderley Park, strain rats showed clear differences in the number of plaque-forming cells in the lymph nodes between arthritic and non-arthritic rats. Differences also occurred between these strains in their response to the production of indirect plaques. The presence of native or denatured type II collage, but not type I collagen, was necessary to increase or maintain, in vitro, the lymphocytes producing anti-collagen antibody and the increase could be inhibited by serum from immunised rats or by colchicine.
Enhancement (by native type II collagen) of the humoral immune response to native type I collagen in the rat.
Both native type II collagen and rabbit IgG were good immunogens in the rat when emulsified in incomplete Freund's adjuvant but native type I collagen and denatured type II collagen were not. Both native type II collagen and rabbit IgG had an enhancing effect upon the production of antibodies to native type I collagen when rats were immunised with a mixture of native type I collagen and either of these immunogens but denatured type II collagen did not have this effect. These immunogens, however, did not enhance the production of antibodies to ovalbumin when emulsified with it. Although both native type II collagen and rabbit IgG showed this enhancing effect with native type I collagen, only rats immunised with native type II collagen or mixtures containing native type II collagen developed arthritis. Thus, a specific immune response to collagen rather than this enhancing effect appears to be necessary for the induction of arthritis.
Native type II collagen-induced arthritis in the rat. II. Relationship between the humoral immune response to native type II collagen and arthritis.
The onset of arthritis in Sprague-Dawley rats occurred between 10-13 days after intradermal injection of collagen when serum IgM and IgG antibody levels to native type II collagen had reached high levels. Although arthritis could be induced in rats immunized with 25-500 microgram native type II collagen in incomplete Freund's adjuvant, higher serum IgM and IgG antibody levels to native type II collagen occurred in arthritic rather than non-arthritic rats irrespective of the immunizing dose of collagen. Studies in 3 different rat strains showed that higher serum antibody levels to native type II collagen were found in the strain with the highest incidence of arthritis. All these findings suggest that these antibodies are one essential for the induction and/or perpetuation of native type II collagen-induced arthritis.