Macrophages that kill glioma cells expressing the membrane form of macrophage colony stimulating factor are resistant to prostaglandin E2 and interleukin-10.
Malignant rat T9 glioma cells retrovirally transduced with the membrane form of macrophage colony stimulating factor (mM-CSF) were killed by bone marrow derived macrophages in 24 h cytotoxicity assays. Prostaglandin E2 (PGE) and interleukin-10 (IL10) were tested for their ability to block this tumoricidal reaction. Only at very high nonphysiological concentrations of PGE (10(-5) and 10(-6) M) was this cytotoxicity inhibited. Use of high doses of theophylline, a phosphodiesterase inhibitor, also prevented macrophages from killing the mM-CSF transduced target cells. IL10 did not alter the killing potential of the mM-CSF tumoricidal macrophages, even though IL10 reduced the production of nitric oxide by macrophages in response to tumor necrosis factor and lipopolysaccharide. IL10 enhanced the growth of bone marrow macrophages suggesting that IL10 has a complex role in the regulation of tumoricidal macrophages. Thus, the mM-CSF may be an ideal agent to treat tumors that utilize either of these two immunosuppressive defense mechanisms that may block other forms of treatment.
Zeineddine
N S
NS
Department of Laboratory Service, Veterans Affairs Medical Center, Long Beach, CA 90822, USA. jadus.martin@long-beach.va.gov
Avina
M D
MD
Williams
C C
CC
Wepsic
H T
HT
Jadus
M R
MR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology; D013806:Theophylline / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D010726:Phosphodiesterase Inhibitors; D011994:Recombinant Proteins; D016753:Interleukin-10; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor; D013806:Theophylline; D015232:Dinoprostone