Korean J Hematol 2003; 38(1):
Published online March 31, 2003
© The Korean Society of Hematology
이식편대종양효과에서 Nitric Oxide의 역할
임창열, 최정기, 손명희, 곽재용
전북대학교 의과대학 내과학교실
The Role of Nitric Oxide in Graft-Versus-Tumor Effect
BACKGROUND : Nitric oxide (NO) synthesis by inducible nitric oxide synthase (iNOS) is induced during graft-versus-host disease (GVHD). It is yet unknown whether NO has any roles in graft-versus-tumor effect (GVT) which is often associated with GVHD. The present study was performed to test the role of NO in GVT.
METHODS: GVT was induced by tail vein injection of C57BL/6J (H-2 b) mouse splenocytes (10 8 cells/mouse) to {C57BL/6J (H-2 b )xBALB/c (H-2(d))} F1 mice bearing Meth-A (H-2d ) ascites tumors.
RESULTS : Induction of GVT increased nitrite production (21.0±4.1μM) and expression of iNOS protein and mRNA by cells derived from ascites. The increased nitrite production was inhibited by N G-monomethyl-L-arginine (MLA). Immunomagnetic depletion of Mac-1+ cells from ascites cells of GVT mice resulted in a 70% decrease in the nitrite production, indicating that macrophages were implicated as a major cellular source of the nitrite production. Interferon-r(IFN r) levels in both serum and ascites fluid were markedly increased during GVT. Induction of GVT in ascites tumor-bearing mice prolonged survival from 9.5±2.2days to 17.6±1.2 days (P<0.001), and increased urinary nitrate excretion up to threefold. MLA administration
effectively inhibited the GVT-induced urinary nitrate excretion and further prolonged the GVT-induced increase in survival from 17.6±1.2days to 23.6±1.9days (P<0.001).
CONCLUSION :
These results indicate that NO synthesis by iNOS is induced in tumor tissues during GVT, and the NO acts as an inhibitor mechanism of GVT.
Keywords Nitric oxide; Graft versus tumor effect; Immunotherapy; Neoplasms; Macrophages; Arginine;
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Korean J Hematol 2003; 38(1): 40-47
Published online March 31, 2003
Copyright © The Korean Society of Hematology.
이식편대종양효과에서 Nitric Oxide의 역할
임창열, 최정기, 손명희, 곽재용
전북대학교 의과대학 내과학교실
The Role of Nitric Oxide in Graft-Versus-Tumor Effect
Chang Yeol Yim, Jung Ki Choi, Myung Hee Sohn, Jae Yong Kwak
Department of Internal Medicine, Chonbuk National University Medical School, Chonju, Korea
Abstract
BACKGROUND : Nitric oxide (NO) synthesis by inducible nitric oxide synthase (iNOS) is induced during graft-versus-host disease (GVHD). It is yet unknown whether NO has any roles in graft-versus-tumor effect (GVT) which is often associated with GVHD. The present study was performed to test the role of NO in GVT.
METHODS: GVT was induced by tail vein injection of C57BL/6J (H-2 b) mouse splenocytes (10 8 cells/mouse) to {C57BL/6J (H-2 b )xBALB/c (H-2(d))} F1 mice bearing Meth-A (H-2d ) ascites tumors.
RESULTS : Induction of GVT increased nitrite production (21.0±4.1μM) and expression of iNOS protein and mRNA by cells derived from ascites. The increased nitrite production was inhibited by N G-monomethyl-L-arginine (MLA). Immunomagnetic depletion of Mac-1+ cells from ascites cells of GVT mice resulted in a 70% decrease in the nitrite production, indicating that macrophages were implicated as a major cellular source of the nitrite production. Interferon-r(IFN r) levels in both serum and ascites fluid were markedly increased during GVT. Induction of GVT in ascites tumor-bearing mice prolonged survival from 9.5±2.2days to 17.6±1.2 days (P<0.001), and increased urinary nitrate excretion up to threefold. MLA administration
effectively inhibited the GVT-induced urinary nitrate excretion and further prolonged the GVT-induced increase in survival from 17.6±1.2days to 23.6±1.9days (P<0.001).
CONCLUSION :
These results indicate that NO synthesis by iNOS is induced in tumor tissues during GVT, and the NO acts as an inhibitor mechanism of GVT.
Keywords: Nitric oxide, Graft versus tumor effect, Immunotherapy, Neoplasms, Macrophages, Arginine,
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