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.