Killing of Histoplasma capsulatum by macrophage colony stimulating factor-treated human monocyte-derived macrophages: Role for reactive oxygen intermediates

* Division of Infectious Disease, Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, 751 South Bascom Avenue, San Jose, CA 95128 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA Correspondence should be sent to Dr D. A. Stevens at the Santa Clara Valley Medical Center. Received October 7, 1994 Accepted February 24, 1995 The interaction of human macrophages with the yeast-form of Histoplasma capsulatum was studied. The use of culture and a short-term assay period instead of microscopy gave direct evidence of the fungicidal activity of human macrophages. The present study reports the novel finding of fungicidal activity of macrophages derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). The induction of fungicidal activity by this cytokine was dose dependent. MCSF at 10000 U/ml was optimal with 73 (SD3)% killing. Inhibition of macrophage killing by superoxide dismutase (SOD), but not catalase (CAT) or N-monomethyl- L -arginine (NMMA), established the role of the superoxide anion in the killing mechanism. The fungistatic activity of MCSF-derived human macrophages in a 24-h assay was also dose dependent and was not inhibited by SOD, CAT or NMMA. MCSF at 10000 U/ml produced optimal macrophage fungistatic activity, 34·6(SD4)%.