Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases.
The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.
D000818:Animals; D017302:Annexins; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D002135:Calcium-Binding Proteins; D002999:Clone Cells; D003882:Dermatomyositis / Q000276:immunology*; D006023:Glycoproteins; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology; D007118:Immunoassay; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010488:Polyarteritis Nodosa / Q000276:immunology*; D011506:Proteins / Q000276:immunology* / Q000302:isolation & purification; D011817:Rabbits; D051381:Rats
D017302:Annexins; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D011506:Proteins; C030958:lipomodulin; D010740:Phospholipases