title: Influence of the pericellular environment on the cells. The role of mucopolysaccharides in the protection of cartilage cells against immune reactions.
abstract: Problems related to rheumatoid arthritis have been investigated by a group at Cambridge using the organ culture technique. Since auto-allergic reactions may be concerned in the chronicity of the disease, the effects of reactive complement-sufficient antisera (AS+C') on embryonic and post-foetal cartilage were examined. The cartilaginous limb bone rudiments enlarged to several times their original volume in control medium, but in the presence of AS+C' they gradually disintegrated, owing to the breakdown of the cartilage matrix; only the superficial cells of the enveloping soft connective tissue were killed, however. Provided breakdown had not advanced too far, the effects of AS+C' were reversible. It was not clear how AS+C' produced these changes, since cartilage matrix is impermeable to molecules as large as the immunoglobulins. To find whether there was a difference in permeability between embryonic and post-foetal cartilage, similar experiments were made on the articular cartilage of young pigs. AS+C' had no effect on pure articular cartilage, and it was shown immunohistochemically that IgG did not penetrate beyond the most superficial layer of cartilage. When, however, the explant was associated with soft connective tissue either as invading marrow or as an adjacent explant of synovium, the cartilage matrix was depleted of proteoglycan; IgG antibodies then entered the cartilage and reacted with the chondrocytes. After a lapse of 8-10 days, collagen also began to break down. If the degradation of collagen was not too extensive, the changes were reversible. Pure cartilage was depleted of proteoglycan by trypsinization and then cultivated in AS+C'. All the chondrocytes reacted with the IgG antibodies. The peripheral cells were killed, but those in the interior survived and rapidly secreted pericellular capsules rich in proteoglycan, which shielded them from further contact with antibodies. In other experiments, pure cartilage was associated with a synovial explant and cultivated in AS+C' for 10 days; this caused severe depletion of the matrix. The synovial tissue was then removed and the isolated cartilage cultured for a further 10 days in either AS+C' or control medium. If mainly proteoglycan had been lost during the primary culture period, breakdown did not continue in AS+C', and sometimes a little new matrix was regenerated, though less than in control medium; if, however, the collagen had been extensively degraded, breakdown continued even in control medium. It is suggested that in both the embryonic and post-foetal cartilage, degradation of the cartilage matrix was due to the enzymatic activity of the associated soft connective tissue which caused a loss first of proteoglycan, which enabled antibodies to reach the chondrocytes, and then of collagen. The possible relevance of these results to the pathogenesis of rheumatoid arthritis is discussed.
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001172:Arthritis, Rheumatoid / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology; D001862:Bone Resorption / Q000276:immunology; D001842:Bone and Bones / Q000378:metabolism / Q000648:ultrastructure; D002356:Cartilage / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D002358:Cartilage, Articular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D005269:Femur; D006025:Glycosaminoglycans / Q000276:immunology*; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000378:metabolism; D013552:Swine; D014357:Trypsin
chemical_list: D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011509:Proteoglycans; D003094:Collagen; D003165:Complement System Proteins; D014357:Trypsin