title: Killing of Histoplasma capsulatum by gamma-interferon-activated human monocyte-derived macrophages: evidence for a superoxide anion-dependent mechanism.
abstract: The interaction of human macrophages with the yeast form of the thermally dimorphic fungal pathogen, Histoplasma capsulatum, was studied. Macrophages derived from monocytes by culture in vitro for 3 days ingested H. capsulatum, but were neither fungicidal or fungistatic. In contrast, when monocytes were exposed to human recombinant gamma-interferon (gamma-IFN) during their differentiation into macrophages, those macrophages were able to reduce the number of ingested or adherent cfu of H. capsulatum by 44-75% in 2 h. Activation of macrophages for fungicidal activity by gamma-IFN was dose dependent and 500-1000 units ml were optimal. Antibody to gamma-IFN abrogated the gamma-IFN activation process. Killing of H. capsulatum by activated macrophages in 2-h assays could be inhibited by superoxide dismutase but not by sodium azide.
authors.affiliation: Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Brummer
authors.forename: N
authors.initials: N
authors.lastname: Kurita
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Miyaji
mesh_terms: D002448:Cell Adhesion; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006658:Histoplasma / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology; D009500:Neutralization Tests; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma; D013482:Superoxide Dismutase