African trypanosomiasis alters prostaglandin production by murine peritoneal macrophages.
Many factors contribute to the severe immunosuppression associated with African trypanosomiasis. Macrophages have been shown to be important target cells which after uptake of parasites, mediate immune dysfunction in vivo. We observed that infection of mice with Trypanosome brucei brucei (clone NIM 6) induces profound changes in arachidonic acid metabolism and prostaglandin (PG) secretion by macrophages. Normal macrophages release more PGI2 than PGE2 and production of both these prostaglandins is stimulated equally by endotoxin (LPS). Macrophages taken from NIM 6 infected mice at the peak of the first parasitaemia, release increased amounts of PGE2 and are hyperresponsive to LPS stimulation, while PGI2 secretion remains normal. As the infection progresses, there is a striking decrease in both basal PGE2 and PGI2 secretion and the ability of macrophages to respond to LPS. By the third week of infection, shortly before death, peritoneal macrophages resemble thioglycollate elicited macrophages in their inability to be stimulated by LPS to synthesize prostaglandins. Infection with a more virulent clone of T. brucei (NIM9) results in suppression of both PGE2 and PGI2 release by day 9 of infection. The increased production of PGE2 by macrophages during the height of infection is likely to contribute to the general immunosuppression associated with African trypanosomiasis.
D000818:Animals; D002448:Cell Adhesion; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D007108:Immune Tolerance; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D014353:Trypanosomiasis, African / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin