Stimulation of macrophage tumoricidal activity by the growth and differentiation factor CSF-1.
The effect of the macrophage growth and differentiation factor CSF-1 on the tumoricidal capacity of murine peritoneal exudate macrophages was investigated. Pretreatment of peptone-elicited macrophages 1 day with 300-1200 U/ml CSF-1 induced moderate killing and greatly stimulated lymphokine (LK)-induced killing of [3H]thymidine-labeled TU5 sarcoma cells to levels above that seen with fresh macrophages. Further addition of CSF-1 at Day 1 at the time of the tumor lysis assay promoted moderate increases in spontaneous and LK-induced activity. CSF-1 did not stimulate freshly harvested exudate macrophages to lyse TU5 targets in the presence or absence of lymphokine (LK) activators. Lipopolysaccharide (LPS) at 0.1-1000 ng/ml did not stimulate cytotoxicity, and the low endotoxin content and the use of polymyxin B and C3H/HeJ mice excluded a role for LPS in these experiments. Incubation of the macrophages with IFN and the myeloid growth factors IL-3 and GM-CSF did not stimulate tumoricidal activity. CSF-1 has been proposed as a therapeutic agent to restore myeloid cell numbers in induced (cancer chemotherapy, bone marrow transplantation, etc.) and natural aplastic anemias. These studies show that CSF-1 also may be useful in combination with LK activators to promote resistance to cancer in mature mononuclear cells. CSF-1 may have similar effects in LK-activated macrophages to enhance resistance to infectious diseases.
D000818:Animals; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007372:Interferons / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008222:Lymphokines / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010537:Peritoneum / Q000166:cytology; D012513:Sarcoma, Experimental / Q000276:immunology
D003115:Colony-Stimulating Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; D007372:Interferons