Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor.
Macrophages derived in vitro from bone marrow progenitors (bone marrow-derived macrophages, BMDMs) using either macrophage colony-stimulating factor (CSF-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as the myelopoietic stimulus display differential functional, morphological, and mRNA phenotypes. The data presented here demonstrate further that CSF-1- and GM-CSF-derived BMDMs differ in immunologic capacity. GM-CSF-derived BMDMs, when compared to CSF-1-derived BMDMs, showed greater cytolytic activity against tumor necrosis factor alpha (TNF-alpha)-resistant, but not TNF-alpha-sensitive, tumor targets. In contrast, CSF-1-derived BMDMs produced nitrite in response to lipopolysaccharide (LPS) alone, whereas GM-CSF-derived BMDMs required interferon gamma plus LPS treatment. The two BMDM populations also showed differential sensitivities to LPS for secretion of TNF-alpha and nitrite, but the maximal inducible amounts of these factors and prostaglandin E2 were similar between the BMDM populations. Lastly, GM-CSF-derived but not CSF-1-derived BMDMs showed an L-arginine-dependent listeriacidal activity. These results show that the functional heterogeneity of CSF-1- and GM-CSF-derived macrophages is limited and appears to result largely from differences in the activational signals required by each BMDM population to elicit a given function.
Rutherford
M S
MS
Department of Animal Sciences, University of Illinois, Urbana-Champaign.
Schook
L B
LB
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001770:Blood Bactericidal Activity; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007121:Immunocompetence / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000502:physiology; D008087:Listeria / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D000907:Antibodies, Bacterial; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone