Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells

doi:10.1084/jem.170.5.1769

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Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells

RD Curran, TR Billiar, DJ Stuehr, K Hofmann and RL Simmons
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.

A metabolic pathway by which L-arginine (L-arg) is converted to the biologically active compound NO. has recently been described in macrophages (M phi) and endothelial cells. This report demonstrates that transferable products from activated Kupffer cells (KC) induce the conversion of large quantities of L-arg to nitrogen oxides within hepatocytes (HC). In M phi and endothelial cells, citrulline and NO2- /NO3- are the stable endproducts of this metabolic pathway. In contrast, HC L-arg metabolism resulted in significantly greater production of NO2-/NO3- than citrulline. The generation of NO. within HC was associated with a concurrent decrease in total protein synthesis.
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Hoffman, R. A. (2000). Intraepithelial lymphocytes coinduce nitric oxide synthase in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G886-G894 [Abstract] [Full Text]
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Matsumoto, H., Nishitani, Y., Minowa, Y., Fukui, Y. (2000). ROLE OF KUPFFER CELLS IN THE RELEASE OF NITRIC OXIDE AND CHANGE OF PORTAL PRESSURE AFTER ETHANOL PERFUSION IN THE RAT LIVER. Alcohol Alcohol 35: 31-34 [Abstract] [Full Text]
Tirmenstein, M. A., Nicholls-Grzemski, F. A., Schmittgen, T. D., Zakrajsek, B. A., Fariss, M. W. (2000). Characterization of Nitric Oxide Production following Isolation of Rat Hepatocytes. Toxicol Sci 53: 56-62 [Abstract] [Full Text]
Brunet, L. R., Beall, M., Dunne, D. W., Pearce, E. J. (1999). Nitric Oxide and the Th2 Response Combine to Prevent Severe Hepatic Damage During Schistosoma mansoni Infection. J. Immunol. 163: 4976-4984 [Abstract] [Full Text]
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Lysiak, J. J., Hussaini, I. M., Webb, D. J., Glass, W. F. , II, Allietta, M., Gonias, S. L. (1995). alpha(2)-Macroglobulin Functions as a Cytokine Carrier to Induce Nitric Oxide Synthesis and Cause Nitric Oxide-dependent Cytotoxicity in the RAW 264.7 Macrophage Cell Line. J. Biol. Chem. 270: 21919-21927 [Abstract] [Full Text]
Fukatsu, K., Saito, H., Fukushima, R., Inoue, T., Lin, M.-T., Inaba, T., Muto, T. (1995). Detrimental Effects of a Nitric Oxide Synthase Inhibitor (N-{omega}-Nitro-L-Arginine-Methyl-Ester) in a Murine Sepsis Model. Arch Surg 130: 410-414 [Abstract]
Minnard, E. A., Shou, J., Naama, H., Cech, A., Gallagher, H., Daly, J. M. (1994). Inhibition of Nitric Oxide Synthesis Is Detrimental During Endotoxemia. Arch Surg 129: 142-148 [Abstract]
Robertson, F. M., Offner, P. J., Ciceri, D. P., Becker, W. K., Pruitt, B. A. Jr (1994). Detrimental Hemodynamic Effects of Nitric Oxide Synthase Inhibition in Septic Shock. Arch Surg 129: 149-156 [Abstract]
Geller, D. A., Freeswick, P. D., Nguyen, D., Nussler, A. K., Silvio, M. D., Shapiro, R. A., Wang, S. C., Simmons, R. L., Billiar, T. R. (1994). Differential Induction of Nitric Oxide Synthase in Hepatocytes During Endotoxemia and the Acute-Phase Response. Arch Surg 129: 165-171 [Abstract]
Geller, D. A., Billiar, T. R. (1993). Should Surgeons Clone Genes? The Strategy Behind the Cloning of the Human Inducible Nitric Oxide Synthase Gene. Arch Surg 128: 1212-1220 [Abstract]
Frederick, J. A., Hasselgren, P. O., Davis, S., Higashiguchi, T., Jacob, T. D., Fischer, J. E. (1993). Nitric Oxide May Upregulate In Vivo Hepatic Protein Synthesis During Endotoxemia. Arch Surg 128: 152-157 [Abstract]
Billiar, T. R., Curran, R. D., Williams, D. L., Kispert, P. H. (1992). Liver Nonparenchymal Cells Are Stimulated to Provide Interleukin 6 for Induction of the Hepatic Acute-Phase Response in Endotoxemia but Not in Remote Localized Inflammation. Arch Surg 127: 31-37 [Abstract]
Stadler, J., Curran, R. D., Ochoa, J. B., Harbrecht, B. G., Hoffman, R. A., Simmons, R. L., Billiar, T. R. (1991). Effect of Endogenous Nitric Oxide on Mitochondrial Respiration of Rat Hepatocytes In Vitro and In Vivo. Arch Surg 126: 186-191 [Abstract]
Billiar, T. R., Curran, R. D. (1990). Kupffer Cell and Hepatocyte Interactions: A Brief Overview. JPEN J Parenter Enteral Nutr 14: 175S-180S