Killing of Histoplasma capsulatum by gamma-interferon-activated human monocyte-derived macrophages: evidence for a superoxide anion-dependent mechanism.
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.
Brummer
E
E
Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Kurita
N
N
Yoshida
S
S
Nishimura
K
K
Miyaji
M
M
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*
D011994:Recombinant Proteins; D013481:Superoxides; D007371:Interferon-gamma; D013482:Superoxide Dismutase