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HUMAN ALVEOLAR AND PERITONEAL MACROPHAGES MEDIATE FUNGISTASIS INDEPENDENTLY OF L-ARGININE OXIDATION TO NITRITE OR NITRATE
Citation:
Cameron, M., D. Granger, J. Weinberg, W. Kozumbo, AND H. Koren. HUMAN ALVEOLAR AND PERITONEAL MACROPHAGES MEDIATE FUNGISTASIS INDEPENDENTLY OF L-ARGININE OXIDATION TO NITRITE OR NITRATE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/520 (NTIS PB91206920).
Description:
Human alveolar macrophages (HAM) from 28 normal volunteers were found to inhibit replication of Cryptoccous neoformans. onditions under which fungistasis occurred were different than those required for mouse peritoneal macrophage-mediated fungi stasis. nhibition of fungal replication by mouse peritoneal macrophages (MPM) requires that the macrophages are activated and that the cocultures of C.neoformans and macrophages be done in the presence of serum, L-arginine, and endotoxin. uring MPM-mediated fungitasis and tumor cell killing, L-arginine is oxidized to NO2-, NO3-, MPM have arginase activity that converts L-arginine to L-ornithine and urea. AM-mediated fungi stasis was similar to that mediated by MPM in terms of the serum requirement, but HAM did not require L-arginine or endotoxic. AM did not product NO2-or NO3- detectable by colorimetric and bioassay, nor did HAM produce L-citrulline or L-ornithine from 14C-radiolabeled L=arginine as detectable by reverse-phase HPLC of macrophage-C, neoformans coculture supernatants. AM had no detectable arginase activity, hence there was no evidence for L-arginine nitrogen metabolism in HAM. AM-mediated fungi stasis was not enhanced by endotoxin or by recombinant human interferon-y (rHIFN-y). he combination of endotoxin and rHIFN-y inhibited the fungistatic effect of HAM. uman peritoneal macrophages (HPM) from women undergoing laparoscopy were tested for fungi stasis and L-arginine nitrogen oxidation. artial inhibition of cryptococcal replication occurred; however, there was no evidence of L-arginine metabolism to NO2- or NO3-. he absence of L-arginine-dependent nitrogen oxidation in HAM and HPM, compared to MPM, during conditions under which fungi stasis occurs suggests that this phenomenon is species specific rather than specific to the tissue origin of the macrophages.