In vivo administration of recombinant macrophage colony-stimulating factor induces macrophage-mediated antibody-dependent cytotoxicity of tumor cells.
Macrophage colony-stimulating factor (M-CSF) has been previously shown to facilitate the in vitro survival and differentiation of mononuclear phagocytes. We assessed whether M-CSF administration in vivo could induce macrophages capable of killing tumor via an antibody-dependent mechanism. C57BL/6 mice were given intraperitoneal M-CSF, and peritoneal macrophages were assayed for their ability to kill fluorochrome-labeled R1.1 thymoma cells in vitro in the presence or absence of target-specific antibody. Two-color flow cytometry was used in measuring tumor ingestion by macrophages; macrophages from M-CSF-treated mice eliminated greater than 90% of R1.1 thymoma target within 24 hours, while macrophages from saline-treated controls were ineffective. R1.1 tumor elimination by macrophages depended on the presence of target-specific antibody. These are the first studies that demonstrate the in vivo induction, by M-CSF, of macrophages directly capable of ingesting antibody-conjugated tumor cells.
Sanda
M G
MG
Surgery Branch, National Institutes of Health, Bethesda, Maryland 20892.
Bolton
E
E
Mulé
J J
JJ
Rosenberg
S A
SA
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D005260:Female; D007167:Immunotherapy; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor