Alterations in murine macrophage arachidonic acid metabolism following ingestion of nonviable Histoplasma capsulatum

Abstract

The effect of ingestion of heat-killed Histoplasma capsulatum yeast cells on the metabolism of arachidonic acid (20:4) to prostenoids and leukotrienes was examined in murine peritoneal macrophages (Mφs). H. capsulatum- containing Mφs exhibited a metabolite profile similar to that of zymosan- challenged phagocytes; however, there were differences with respect to the relative and total amounts of products produced. While proteose peptone- elicited Mφs exposed to H. capsulatum released quantitatively less prostaglandin E2 (PGE2) and leukotriene C4 than zymosan-treated Mφs, they metabolized a greater percentage of total product to prostenoids. In addition, whereas in vitro priming with gamma interferon increased both the PGE2 and leukotriene C4 contents of zymosan-stimulated Mφ supernatants, similarly primed Mφs challenged with H. capsulatum selectively increased only PGE2 production. The immunosuppressive effect of a relative excess of prostenoids in H. capsulatum-containing Mφs may contribute to the overall disturbance in cell-mediated immunity characteristic of disseminated histoplasmosis.