Role of colony-stimulating factor-1 in macrophage activation in tumor-bearing mice.
We previously reported a dramatically increased number of macrophages in tumor-bearing mice. In this study, we investigated the involvement of CSF in that phenomenon. CSF-1 responding cells as macrophages precursors increased significantly in number in the spleens of tumor-bearing mice as compared with those in normal mice. Splenic cells and sera from the tumor-bearing mice respectively expressed CSF-1 in mRNA and serum protein levels, but failed to express the other CSF (granulocyte-macrophage-CSF or IL-3). Nonadherent splenic mononuclear cells (< 0.5% macrophages) from normal mice proliferated and differentiated into mature macrophages in culture within 7 days with recombinant mouse CSF-1 (rCSF-1). Both macrophages harvested from tumor-bearing mice and those activated in vitro with rCSF-1 expressed mostly Mac-1, -2 (and -3) Ag, showed yeast phagocytosis, produced IL-1 but not IL-2 or IL-3, and displayed potent cytotoxicity against NK cell resistant Meth-A tumor cells. These macrophages also expressed lipocortin I mRNA and secreted lipocortin I protein, and suppressed mitogenic responses of splenic lymphocytes. rCSF-1-activated macrophages derived from nonadherent splenic cells expressed both CSF-1 and CSF-1 receptor (c-fms) mRNA. Administration of rCSF-1 into normal mice induced hemopoietic and immunologic alternations similar to those observed in tumor-bearing mice. These results suggest that CSF-1 is involved in the dramatic increase of macrophages in tumor-bearing mice, possibly through an autocrine or paracrine loop.
D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D037502:Galectin 3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D015345:Oligonucleotide Probes; D012313:RNA / Q000032:analysis / Q000096:biosynthesis; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D017305:Annexin A1; D000943:Antigens, Differentiation; D037502:Galectin 3; D007375:Interleukin-1; D016177:Macrophage-1 Antigen; D015345:Oligonucleotide Probes; D016184:Receptors, Colony-Stimulating Factor; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor