| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 149, Issue 8 2709-2714, Copyright © 1992 by American Association of Immunologists
ARTICLES |
CD Mills, J Shearer, R Evans and MD Caldwell
Department of Surgery, University of Minnesota, Minneapolis 55455.
The potential of the immune system to inhibit or stimulate tumor growth is a vivid example of the "two-edged sword" nature of immune responses. Our results provide evidence that this dual capacity can be attributed, in part, to the dual pathways of arginine metabolism exhibited by intratumor macrophages. Specifically, i.p. tumor rejection in P815- preimmunized mice is accompanied by an upshift in intratumor macrophage arginine metabolism to the nitric oxide (NO) synthase pathway that yields citrulline and NO. A rapid and marked local increase in IFN- gamma (both mRNA and protein) in preimmunized mice during tumor rejection suggests that this cytokine plays a role in up-regulating nitric oxide production in vivo. Unlike tumor rejection, progressive i.p. P815 tumor growth in naive mice is associated with a marked decline in the production of citruline/NO by intratumor macrophages. Examination of macrophage arginine metabolism via arginase revealed a pattern opposite that of NO synthase. The local production of ornithine/urea markedly increases during progressive tumor growth whereas arginase activity decreases during tumor rejection. Inasmuch as nitric oxide inhibits tumor cell replication whereas ornithine is the precursor of polyamines required for cell replication, these results are consistent with the conclusion that the pathway macrophages use to metabolize arginine can influence the type of host immune responses against cancer and other conditions.
This article has been cited by other articles:
|
|
 |
|
  C. Guruvayoorappan Tumor Versus Tumor-Associated Macrophages: How Hot is the Link? Integr Cancer Ther, June 1, 2008; 7(2): 90 - 95. [Abstract] [PDF]
|
|
|
|
 |
|
 E. F. Redente, D. J. Orlicky, R. J. Bouchard, and A. M. Malkinson Tumor Signaling to the Bone Marrow Changes the Phenotype of Monocytes and Pulmonary Macrophages during Urethane-Induced Primary Lung Tumorigenesis in A/J Mice Am. J. Pathol., February 1, 2007; 170(2): 693 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Van Ginderachter, S. Meerschaut, Y. Liu, L. Brys, K. De Groeve, G. Hassanzadeh Ghassabeh, G. Raes, and P. De Baetselier Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer Blood, July 15, 2006; 108(2): 525 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, J. A. Van Ginderachter, L. Brys, P. De Baetselier, G. Raes, and A. B. Geldhof Nitric Oxide-Independent CTL Suppression during Tumor Progression: Association with Arginase-Producing (M2) Myeloid Cells J. Immunol., May 15, 2003; 170(10): 5064 - 5074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Raes, P. De Baetselier, W. Noel, A. Beschin, F. Brombacher, and G. Hassanzadeh Gh. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages J. Leukoc. Biol., April 1, 2002; 71(4): 597 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-I Chang, J. C. Liao, and L. Kuo Macrophage Arginase Promotes Tumor Cell Growth and Suppresses Nitric Oxide-mediated Tumor Cytotoxicity Cancer Res., February 1, 2001; 61(3): 1100 - 1106. [Abstract] [Full Text]
|
|
|
|
|
|
Y.-Z. Wu, J.-H. Hong, H.-H. Huang, G. J. Dougherty, W. H. McBride, and C.-S. Chiang Mechanisms mediating the effects of IL-3 gene expression on tumor growth J. Leukoc. Biol., December 1, 2000; 68(6): 890 - 896. [Abstract] [Full Text]
|
|
|
|
|
|
C. D. Mills, K. Kincaid, J. M. Alt, M. J. Heilman, and A. M. Hill M-1/M-2 Macrophages and the Th1/Th2 Paradigm J. Immunol., June 15, 2000; 164(12): 6166 - 6173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Singh, S. Pervin, A. Karimi, S. Cederbaum, and G. Chaudhuri Arginase Activity in Human Breast Cancer Cell Lines: N{{omega}}-Hydroxy-L-arginine Selectively Inhibits Cell Proliferation and Induces Apoptosis in MDA-MB-468 Cells Cancer Res., June 1, 2000; 60(12): 3305 - 3312. [Abstract] [Full Text]
|
|
|
|
|
|
M. Medot-Pirenne, M. J. Heilman, M. Saxena, P. E. McDermott, and C. D. Mills Augmentation of an Antitumor CTL Response In Vivo by Inhibition of Suppressor Macrophage Nitric Oxide J. Immunol., December 1, 1999; 163(11): 5877 - 5882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-W. Hwang, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, M. Hara, and S. Sasayama FTY720, a New Immunosuppressant, Promotes Long-Term Graft Survival and Inhibits the Progression of Graft Coronary Artery Disease in a Murine Model of Cardiac Transplantation Circulation, September 21, 1999; 100(12): 1322 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wahlsten, C. D. Mills, and S. Ramakrishnan Antitumor Response Elicited by a Superantigen- Transmembrane Sequence Fusion Protein Anchored onto Tumor Cells J. Immunol., December 15, 1998; 161(12): 6761 - 6767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Munder, K. Eichmann, and M. Modolell Alternative Metabolic States in Murine Macrophages Reflected by the Nitric Oxide Synthase/Arginase Balance: Competitive Regulation by CD4+ T Cells Correlates with Th1/Th2 Phenotype J. Immunol., June 1, 1998; 160(11): 5347 - 5354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-I Chang, J. C. Liao, and L. Kuo Arginase modulates nitric oxide production in activated macrophages Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H342 - H348. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
