Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar macrophages.
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P less than 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P less than 0.01) less activity than alveolar macrophages at doses of 1000-5000 units/ml. Maximal activity in alveolar macrophages occurred 72-96 h after exposure to 1000-5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor alpha and interleukin 1 beta were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1 beta secretion was not enhanced by GM-CSF; however, tumor necrosis factor alpha secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1 beta or tumor necrosis factor alpha.
Thomassen
M J
MJ
Department of Pulmonary Disease, Cleveland Clinic Foundation, Ohio 44195-5038.
Barna
B P
BP
Rankin
D
D
Wiedemann
H P
HP
Ahmad
M
M
D000328:Adult; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D011650:Pulmonary Alveoli / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor