Rapid killing of actinomycin D-treated tumor cells by mononuclear phagocytes: characterization of effector cells in mice.
Pretreatment with Actinomycin D (Act D, 1 microgram/ml for 3 hr) rendered WEHI 164 tumor cells susceptible to killing by mouse resident or peptone-induced peritoneal exudate cells (PEC) in a 6-hr 51Cr release assay. Cytotoxicity was attributed to cells of the monocyte macrophage lineage on the basis of tissue distribution, separation by adherence on plastic and carbonyl iron, membrane antigens, and expression in mice with defective T cell- or NK cell-mediated immunity. Macrophages from four strains of mice (C3H/HeJ, A/J, P/J, C57B1/10 ScCR) previously shown to have defective "classical" nonspecific tumoricidal activity were examined for killing of Act-D-treated WEHI 164 cells. C3H/HeJ peritoneal macrophages had little or no DDCC, whereas cells from A/J, P/J, and C57B1/10 ScCR mice had normal levels of this reactivity. Tumor cells exposed to ActD were heterogenous in their susceptibility to killing by PEC, with five lines showing significant, though variable, lysis, whereas 12 tumor lines, normal fibroblasts, and lymphoblasts were not appreciably killed under the same conditions. Macrophage-mediated DDCC was also detectable in a colony assay. DDCC could explain how macrophages contribute to the antitumor activity of selected chemotherapeutic agents in murine tumor models.
Colotta
F
F
Polentarutti
N
N
Bersani
L
L
Poli
G
G
Mantovani
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology*; D005347:Fibroblasts; D006412:Hematopoietic Stem Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental; D010529:Peritoneal Cavity / Q000166:cytology; D011650:Pulmonary Alveoli / Q000166:cytology; D013045:Species Specificity; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D003609:Dactinomycin