concanavalin-a and Cartilage-Diseases

Rat femoral head cartilages (FHCs) in culture for six days retained their glycosaminoglycan (GAG) content and were not affected by recombinant human interleukin-la (IL-1), conditioned media from concanavalin-A stimulation of sensitized lymphocytes (lymphocyte media), or conditioned media from lymphokine-stimulated macrophages (macrophage media). Similarly FHCs cultured with macrophages in the presence of IL-1, lymphocyte medium or macrophage medium did not suffer a loss of GAG. However, FHCs cultured with fibroblasts showed a substantial loss of GAG. This fibroblast-mediated cartilage degradation was significantly increased by IL-1 and macrophage media respectively. Stimulation of fibroblasts by lymphocyte media failed to increase the loss of GAG. It is proposed that cartilage degradation in inflammatory joint disease is brought about by a sequential cell-to-cell interaction via cytokines leading ultimately to stimulation of fibroblast-mediated cartilage degradation.

Topics: Animals; Cartilage; Cartilage Diseases; Cell Communication; Cells, Cultured; Concanavalin A; Culture Media; Fibroblasts; Glycosaminoglycans; Lymphocytes; Lymphokines; Macrophages; Male; Rats; Rats, Inbred Lew; Rats, Inbred Strains

Individuals with cartilage-hair hypoplasia (CHH), an autosomal recessive form of short-limbed dwarfism, have markedly reduced lymphocyte proliferative responses and cutaneous delayed hypersensitivity reactions, but normal humoral immunity. In the present study we investigated the cellular basis of the immunodeficiency in CHH. Defective lymphocyte proliferation could be due to a) an imbalance of immunoregulatory lymphocyte subpopulations, b) defective accessory cell function, or c) an intrinsic cellular defect in lymphocytes from CHH individuals. The absolute numbers of B cells and immunoregulatory (OKT4+, OKT8+) T cells were markedly diminished, but the proportions of these populations were the same as in the normal controls. OKM1+ lymphocytes were increased in proportion, and OKM1+ macrophages had normal adherence, helper, and phagocytic properties. Co-culture experiments failed to reveal any evidence of suppression by CHH mononuclear cells. CHH lymphocytes could not be stimulated to proliferate normally with B and T cell activators, mitogenic monoclonal antibody (OKT3), allogeneic cells, or chemical activators (Ca++ ionophore A23187 and phorbol myristate acetate). Fibroblasts from three CHH individuals also proliferated at a significantly decreased rate, compared to two normal lines. These results demonstrate a selective loss of B and T lymphocytes in CHH, as well as an intrinsic proliferative defect in CHH lymphocytes distal to the initial events in the lymphocyte activation sequence. These findings in CHH fibroblasts and lymphocytes may reflect a generalized defect present in multiple cell types in CHH.

Topics: Adult; Antibodies, Monoclonal; Calcimycin; Cartilage Diseases; Cell Division; Concanavalin A; Dwarfism; Fibroblasts; Hair Diseases; Humans; Immunity, Cellular; Lymphocyte Activation; Lymphocytes; Middle Aged; Phytohemagglutinins; Staphylococcus aureus