Arachidonic acid metabolism in murine leishmaniasis (Donovani): ex-vivo evidence for increased cyclooxygenase and 5-lipoxygenase activity in spleen cells.
This study examined the metabolism of arachidonic acid (20:4) by splenic mononuclear cells from BALB/c mice infected with Leishmania donovani. Spleen cells removed from mice after either 4 or 8 weeks of infection and cultured in the presence of phytohemagglutinin (PHA) incorporated 60-70% less [3H]thymidine and synthesized 2- to 5-fold more prostaglandin E2 than did spleen cells from normal mice. Inhibition of cyclooxygenation by sodium meclofenamate was associated with restoration of PHA-induced spleen cell blastogenesis. Thin-layer chromatography of spleen cell extracts showed that PHA-stimulated spleen cells from infected animals synthesized 54 and 27% more 5-hydroxyeicosatetraenoic acid (5-HETE) and 12/15-HETE respectively, when compared to spleen cells from noninfected mice. Culture medium of spleen cells from infected mice also contained 25% more immunoreactive leukotriene C4. Nordihydroguaiaretic acid (3 microM) reduced spleen cell synthesis of 12/15-HETE while minimally affecting 5-HETE production. These data indicated that increased cyclooxygenase and lipoxygenase activities in spleen cells from mice infected with L. donovani resulted in the generation of 20:4 metabolites with the capability of altering T-lymphocyte function.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D006224:Cricetinae; D015232:Dinoprostone; D005260:Female; D007898:Leishmaniasis, Visceral / Q000201:enzymology*; D008084:Lipoxygenase / Q000378:metabolism*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011458:Prostaglandins E / Q000032:analysis; D013154:Spleen / Q000201:enzymology*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone