title: Recombinant murine gamma interferon stimulates macrophages of the RAW cell line to inhibit intracellular growth of Histoplasma capsulatum.
abstract: Macrophages of the RAW 264.7 cell line, activated by pretreatment with recombinant murine gamma interferon, inhibit the intracellular growth of Histoplasma capsulatum. Growth inhibition occurred by a mechanism that was operative only when L-Arg metabolism was allowed to occur. When activated macrophages were cultured in the absence of L-Arg or in the presence of NG-monomethyl-L-Arg, a competitive inhibitor of L-Arg metabolism, activation to the antihistoplasma growth-inhibitory state did not occur. An increase in levels of NO2-, an end product of L-Arg metabolism, was detected only after activation of RAW 264.7 cells to the growth-inhibitory state. In contrast, only baseline levels of NO2- were detected when L-Arg was excluded or when NG-monomethyl-L-Arg was added to the culture medium. Nitric oxide (NO.), a reactive intermediate product of L-Arg metabolism, was implicated as the relevant antihistoplasma effector molecule. When H. capsulatum yeast cells were cultured for 24 to 28 h in a system designed to generate soluble NO., a dose-dependent cytotoxic effect was observed.
authors.affiliation: Department of Microbiology and Immunology, UCLA School of Medicine 90024.
authors.forename: L T
authors.initials: LT
authors.lastname: Nakamura
authors.forename: B A
authors.initials: BA
authors.lastname: Wu-Hsieh
authors.forename: D H
authors.initials: DH
authors.lastname: Howard
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D006658:Histoplasma / Q000187:drug effects / Q000254:growth & development* / Q000472:pathogenicity; D006660:Histoplasmosis / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D011994:Recombinant Proteins
chemical_list: D009566:Nitrates; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine