Smith P D, Lamerson C L, Banks S M, Saini S S, Wahl L M, Calderone R A, Wahl S M
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
J Infect Dis. 1990 May;161(5):999-1005. doi: 10.1093/infdis/161.5.999.
The ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to augment the fungicidal activity of human monocytes for Candida albicans was evaluated. Purified human monocytes cultured with [3H]leucine-labeled C. albicans caused a dose-dependent release of the [3H]leucine. The amount of [3H]leucine released correlated with a decrease in the number of viable yeast colonies. Monocyte cytotoxicity for C. albicans was reduced by superoxide dismutase and catalase and by inhibitors of myeloperoxidase and scavengers of hydroxyl radical and single oxygen, consistent with monocyte candidacidal activity being partly dependent upon products of oxidative metabolism. Monocytes incubated with rhGM-CSF produced more superoxide anion (O2-) spontaneously and after stimulation than control monocytes (P less than .05). Enhanced O2- production was dose-dependent and specific for rhGM-CSF and could be inhibited by antibody to rhGM-CSF. In association with rhGM-CSF-induced production of O2-, the cytokine enhanced cytotoxic activity for C. albicans. These findings indicate that rhGM-CSF stimulates human monocyte fungicidal activity for C. albicans.
评估了重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)增强人单核细胞对白色念珠菌杀菌活性的能力。用[3H]亮氨酸标记的白色念珠菌培养纯化的人单核细胞,导致[3H]亮氨酸呈剂量依赖性释放。释放的[3H]亮氨酸量与活酵母菌落数量的减少相关。超氧化物歧化酶、过氧化氢酶、髓过氧化物酶抑制剂以及羟自由基和单线态氧清除剂可降低单核细胞对白色念珠菌的细胞毒性,这表明单核细胞的杀念珠菌活性部分依赖于氧化代谢产物。与对照单核细胞相比,用rhGM-CSF孵育的单核细胞自发产生和刺激后产生的超氧阴离子(O2-)更多(P小于0.05)。O2-产生的增强呈剂量依赖性且对rhGM-CSF具有特异性,并可被抗rhGM-CSF抗体抑制。与rhGM-CSF诱导的O2-产生相关,该细胞因子增强了对白色念珠菌的细胞毒性活性。这些发现表明,rhGM-CSF刺激人单核细胞对白色念珠菌的杀菌活性。