Alterations in murine macrophage arachidonic acid metabolism following ingestion of nonviable Histoplasma capsulatum.
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 (M phi s). H. capsulatum-containing M phi s 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 M phi s exposed to H. capsulatum released quantitatively less prostaglandin E2 (PGE2) and leukotriene C4 than zymosan-treated M phi s, 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 M phi supernatants, similarly primed M phi s challenged with H. capsulatum selectively increased only PGE2 production. The immunosuppressive effect of a relative excess of prostenoids in H. capsulatum-containing M phi s may contribute to the overall disturbance in cell-mediated immunity characteristic of disseminated histoplasmosis.
Wolf
J E
JE
Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Massof
S E
SE
Peters
S P
SP
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D015232:Dinoprostone / Q000096:biosynthesis; D006660:Histoplasmosis / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008084:Lipoxygenase / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008806:Mice, Inbred AKR; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011863:Radioimmunoassay; D013189:SRS-A / Q000096:biosynthesis
D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone