Synthesis of prostaglandin E by peritoneal macrophages from NZB/W mice

Abstract

Peritoneal macrophages from NZB/W (murine lupus) mice spontaneously produce less prostaglandin E (PGE) than peritoneal macrophages from immunologically normal mice. Reduced PGE synthesis is seen as early as 2 months of age and becomes more profound as disease progresses. It is suggested that impaired production of PGE by peritoneal macrophages from NZB/W mice may account in part for abnormal macrophage function observed in these animals. Studies of New Zealand mice strains have been of interest and value in the understanding of immunologically related diseases. The F 1 hybrid (NZB/W) from the cross between NZB × NZW mice spontaneously develops a disease similar to human systemic lupus erythematosus (SLE). Murine lupus is characterized by appearance of antibodies to nuclear antigens (1–4) and the development of immune complex-mediated glomerulonephritis (5). We have shown that animals treated with prostaglandin E 1 (PGE 1) are protected from development of anemia, nephritis and death (6). Treatment also prevents glomerular deposition of immunoglobulins and complement and enhances cell mediated responses (7–9). Treatment has no effect on titers of circulating antibodies to nuclear constituents (9), but does reduce the level of antibody to gp70, a retrovirus coat glycoprotein present in these animals (10). Although the protective effect of PGE 1 in treatment of NZB/W mice has been confirmed and expanded in a number of studies (10–13), the precise mechanisms responsible for this therapeutic effect have not been defined. Among cells involved in immune responses, macrophages are the major producers of prostaglandins. In an attempt to further understand how exogenous PGE might suppress disease in NZB/W mice it became important to determine whether exogenous PGE synthesis is altered in macrophages from NZB/W mice. In the work presented here, we show that peritoneal macrophages from NZB/W mice spontaneously produce less PGE than macrophages from immunologically normal mice. Depressed PGE synthesis is seen as early as 2 months of age.