title: Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.
abstract: The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10% dialyzed fetal bovine serum. Fungistasis was measured using electronic particle counting after lysis of macrophages with detergent. Macrophage fungistasis failed in medium lacking only L-arginine. Complete fungistasis was restored by L-arginine; restoration was concentration dependent, maximal at 200 microM. Deletion of all other essential amino acids did not abrogate fungistasis provided that L-arginine was present. Of twenty guanido compounds, including D-arginine, only three (L-arginine, L-homoarginine, and L-arginine methylester) supported fungistasis. Known activators or mediators of macrophage cytotoxicity (endotoxin, interferon gamma, tumor necrosis factor) did not replace L-arginine for CM-mediated fungistasis. The guanido analogue NG-monomethyl-L-arginine was a potent competitive inhibitor of CM-mediated fungistasis giving 50% inhibition at an inhibitor/L-arginine ratio of 1:27. Although CM completely blocked fungal reproduction via an L-arginine-dependent mechanism, the majority of the dormant fungi remained viable. Thus, this mechanism is viewed as a microbiostatic process similar or identical to the tumoristatic effect of macrophages. This suggests the production of a broad spectrum biostatic metabolite(s) upon consumption of L-arginine by cytotoxic macrophages.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: D L
authors.initials: DL
authors.lastname: Granger
authors.forename: J B
authors.initials: JB
authors.lastname: Hibbs
authors.forename: J R
authors.initials: JR
authors.lastname: Perfect
authors.forename: D T
authors.initials: DT
authors.lastname: Durack
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D003454:Cryptococcus / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice
chemical_list: D001120:Arginine