Altered immune complex-induced prostaglandin production in human and murine lupus.
Monocytes were isolated by adherence from peripheral blood of normal controls and patients with systemic lupus erythematosus who were in the inactive and untreated phase of the disease. Peritoneal macrophages were isolated by adherence from NZB/W, BXSB and C57 control mice. These mononuclear phagocytes were cultured for 24 hours in the presence or absence of immune complexes (IC), after which prostaglandin E (PGE) levels were measured by RIA. Among the humans, normal monocytes responded to in vitro IC treatment with a 6.3-fold increase in PGE output and monocytes from SLE patients displayed only a 3-fold increase in PGE output. Baseline levels showed no difference. Circulating IC levels, as determined by the Raji cell assay, were highly elevated (greater than 6400 ug/ml) in all but one SLE patient. The murine lupus models compared to controls showed similar differences. C57Bl/nJ mice showed a significant increase of PGE production when stimulated with increasing amounts of IC. BXSB and NAB/W mice, however, showed no such increase. It is hypothesized that defective Fc receptor function on monocytes of patients with SLE prevent IC-induced production of normal amounts of PGE.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D001202:Ascitic Fluid / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D009000:Monocytes / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*
D000936:Antigen-Antibody Complex; D011458:Prostaglandins E