Nitric oxide synthesis contributes to inhibition of graft-versus-tumor-effects against intraperitoneal Meth A tumor.
The role of nitric oxide (NO) in graft-versus-tumor-effect (GVT) was evaluated in the present study. GVT was induced by intravenous injection of C57BL/6J (H-2b) mouse splenocytes to {C57BL/6J (H-2b) x BALB/c (H-2d)} F1 mice bearing Meth A (H-2d) ascites tumors. Induction of GVT increased nitrite production and expression of inducible NO synthase by ascites cells. The increased nitrite production was inhibited by NG-monomethyl-L-arginine (MLA). Experiments employing immunomagnetic depletion of Mac-1+ cells from ascites indicated that macrophages were a major cellular source of the nitrite production. Interferon-gamma levels were increased in both serum and ascites fluid during GVT. Induction of GVT prolonged survival of ascites-bearing mice, and increased urinary nitrate excretion. MLA administration inhibited GVT-induced increase in urinary nitrate excretion, and further prolonged GVT-induced increase in survival. These results indicate that NO synthesis is induced in tumors during GVT, and the NO acts as an inhibitor of GVT.
Song
Eun-Kee
EK
Department of Internal Medicine, Chonbuk National University Medical School, Chonju, Chonbuk 561-712, Republic of Korea.
Lee
Na-Ri
NR
Sohn
Myung-Hee
MH
Kwak
Jae-Yong
JY
Yim
Chang-Yeol
CY
D000818:Animals; D001201:Ascites / Q000276:immunology; D015153:Blotting, Western; D003433:Crosses, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000652:urine; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000652:urine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009573:Nitrites; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012313:RNA; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse