|
Sign In to gain access to subscriptions and/or personal tools.
|
Innate Immunity, Vol. 14, No. 1,
51-60 (2008)
DOI: 10.1177/1753425907087267
Clearance of bacterial lipopolysaccharides and lipid A by the liver and the role of arginino-succinate synthase
Motonobu Satoh
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan, moto-sth{at}pharm.teikyo-u.ac.jp
Shingo Ando
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
Takehiro Shinoda
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
Masatoshi Yamazaki
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
The liver is thought to be involved in the systemic clearance and detoxification of lipopolysaccharide (LPS). Argininosuccinate synthase (AS), a liver cytosolic urea cycle enzyme, has been found to bind to and inactivate LPS and lipid A. To elucidate the participation of AS in the clearance of LPS by liver and hepatocytes, we investigated the correlation between AS content and the removal of lipid A and LPS in vivo and in vitro, tracing levels of biological activity. A hepatotoxic model in which mice were injected with CCl4 revealed a significant reduction in lipid A clearance along with liver failure on day 1; total body clearance was changed to 0.534 ml/min from 1.42 ml/min. AS content in liver concomitantly decreased to about half and AS leaked to blood at about 6 µg/ml. Total body clearance of i.v. injected AS was estimated at 0.083 ml/min, which predicted about 24-h leakage of AS after CCl4 injection. The treatment also reduced the clearance of R-type LPSs to a lesser degree the larger its polysaccharide portion. S-type LPS, which has a large O-antigen polysaccharide, exhibited enhancement of clearance on CCl4 treatment. When pretreated in vitro with AS and injected into normal mice, lipid A and R-type LPS showed a similar pattern of clearance of residual activities to the untreated forms, but S-type LPS exhibited enhancement of clearance. Comparison between different strains of mice revealed a correlation of AS content in liver and lipid A clearance, where the higher AS strain C3H/He mice showed a more rapid clearance than the lower AS strains C57BL/6 and BALB/c. Primary spheroid cultures of hepatocytes treated with 0.1 µM dexamethasone and 1 µM glucagon showed about a 2-fold increase in AS amount and a more rapid clearance of LPS from culture medium than untreated cells. These results suggest that AS in hepatocytes may be involved in the process of lipid A and LPS clearance and the extracellular leakage of AS may also participate in the systemic detoxification.
Key Words: Argininosuccinate synthase • clearance • endotoxin • lipid A • liver
References
- Nowotny A. Review of molecular requirements of endotoxic reactions. Rev Infect Dis 1987; 9: 503—511.
- Morrison DC, Ryan JL Bacterial endotoxin and host immune response. Adv Immunol 1983; 28: 293—452.
- Kitchens RL, Munford RS CD14-dependent-internalization of bacterial lipopolysaccharide (LPS) is strongly influenced by LPS aggregation but not by cellular responses to LPS. J Immunol 1998; 160: 1920—1928.[Abstract/Free Full Text]
- Gegner JA, Ulevitch RJ, Tobias PS Lipopolysaccharide (LPS) signal transduction and clearance. Dual roles for LPS binding protein and membrane CD14. J Biol Chem 1995; 270: 5320—5325.[Abstract/Free Full Text]
- Hewett JA, Roth RA Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides. Pharmacol Rev 1993; 45: 382—411.[Medline]
[Order article via Infotrieve]
- Harris HW, Grunfeld C., Feingold KR et al. Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. J Clin Invest 1993; 91: 1028—1034.[Medline]
[Order article via Infotrieve]
- Harris HW, Brady SE, Rapp JH Hepatic endosomal trafficking of lipoprotein-bound endotoxin in rats. Surg Res 2002; 106: 188—195.[CrossRef]
- Macintire DK, Bellhorn TL Bacterial translocation: clinical implications and prevention. Vet Clin North Am Small Anim Pract 2002; 32: 1165—1178.[CrossRef][Medline]
[Order article via Infotrieve]
- Lichtman SM Bacterial translocation in humans. J Pediatr Gastroenterol Nutr 2001; 33:1—10.[CrossRef][Medline]
[Order article via Infotrieve]
- Reynolds JV, Murchan P., Leonard N. et al. Gut barrier failure in experimental obstructive jaundice. J Surg Res 1996; 62: 11—16.[CrossRef][Medline]
[Order article via Infotrieve]
- Kakkos SK, Kirkilesis J., Scopa CD et al. Nonabsorbable antibiotics reduce bacterial and endotoxin translocation in hepatectomised rats. HPB Surg 1997; 10: 283—289.[Medline]
[Order article via Infotrieve]
- Hori Y., Takeyama Y., Ueda T. et al. Impaired transport of lipopolysaccharide across the hepatocytes in rats with ceruleininduced experimental pancreatitis. Pancreas 1998; 16: 148—153.[Medline]
[Order article via Infotrieve]
- Satoh M., Iwahori T., Sugawara N., Yamazaki M. Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid A and inactivates their biological activities. J Endotoxin Res 2006; 12: 21—38.[Medline]
[Order article via Infotrieve]
- Husson A., Brasse-Lagnel C., Fairand A. et al. Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem 2003; 270: 1887—1899.[Medline]
[Order article via Infotrieve]
- Saheki T., Komorizono K., Miura T. et al. Clearance of argininosuccinate synthetase from the circulation in acute liver disease. Clin Biochem 1990; 23: 139—141.[CrossRef][Medline]
[Order article via Infotrieve]
- Satoh M., Adachi K., Suda T. et al. TNF-driven inflammation during mouse liver regeneration after partial hepatectomy and its role in growth regulation of liver. Mol Biother 1991; 3: 136—147.[Medline]
[Order article via Infotrieve]
- Satoh M., Matsumura T., Nakamoto M., Yamazaki M. Inhibition of TNF-triggering activity of lipopolysaccharide by a proteinaceous factor from normal mouse liver extract. J Immunol 1995; 155: 877—885.[Abstract]
- Satoh M., Yamazaki M. Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is suppressed by transforming growth factor β and interleukin 6. J Cell Physiol 1992; 150: 134—139.[CrossRef][Medline]
[Order article via Infotrieve]
- Satoh M., Tsurumaki K., Kagehara H., Yamazaki M. Induction of intratumoral tumor necrosis factor by a synthetic lipid A analog, ONO-4007, with less tolerance in repeated administration and its implication in potent antitumor effects with low toxicity. Cancer Immunol Immunother 2002; 50: 653—662.[CrossRef][Medline]
[Order article via Infotrieve]
- Abu-Absi SF, Friend JR, Hansen LK, Hu WS Structural polarity and functional bile canaliculi in rat hepatocyte spheroids. Exp Cell Res 2002; 274: 56—67.[CrossRef][Medline]
[Order article via Infotrieve]
- Lin RC, Snodgrass PJ, Rabier D. Induction of urea cycle enzymes by glucagon and dexamethasone in monolayer cultures of adult rat hepatocytes. J Biol Chem 1982; 257: 5061—5067.[Free Full Text]
- McCay PB, Lai EK, Poyer JL et al. Oxygen and carbon centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J Biol Chem 1984; 259: 2135—2143.[Abstract/Free Full Text]
- Hasunuma R., Morita H., Tanaka S. et al. Differential clearance and induction of host responses by various administered or released lipopolysaccharides. J Endotoxin Res 2001; 7: 421—429.[CrossRef][Medline]
[Order article via Infotrieve]
- Denlinger LC, Garis KA, Sommer JA et al. Nuclear translocation of NF-
 B in lipopolysaccharide treated macrophages fails to correspond to endotoxicity: evidence suggesting a requirement for a gammainterferon-like signal. Infect Immun 1998; 66: 1638—1647.[Abstract/Free Full Text] - Amura CR, Silverstein R., Morrison DC Mechanisms involved in the pathogenesis of sepsis are not necessarily reflected by in vitro cell activation studies. Infect Immun 1998; 66: 5372—5378.[Abstract/Free Full Text]
- Rietsche ETh, Kirikae T., Schade FU et al. The chemical structure of bacterial endotoxin in relation to bioactivity. Immunobiology 1993; 187: 169—190.[Medline]
[Order article via Infotrieve]
- Kitchens RL, Munford RS CD14-dependent internalization of bacterial lipopolysaccharide (LPS) is strongly influenced by LPS aggregation but not by cellular responses to LPS. J Immunol 1998; 160: 1920—1928.[Abstract/Free Full Text]
- Iovine N., Eastvold J., Elsbach P., Weiss JP, Gioannini TL The carboxyl-terminal domain of closely related endotoxin binding proteins determines the target of protein—lipopolysaccharide complexes. J Biol Chem 2002; 277: 7970—7978.[Abstract/Free Full Text]
- Caccavo D., Afeltra A., Pece S. et al. Lactoferrin—lipidA—lipopolysaccharide interaction: inhibition by anti-human lactoferrin monoclonal antibody AGM 10.14. Infect Immun 1999; 67: 4668—4672.[Abstract/Free Full Text]
- Li CM, Chao HK, Liu YF, Su TS A nonsense mutation is responsible for the RNA-negative phenotype in human citrullinaemia. Eur J Hum Genet 2001; 9: 685—689.[CrossRef][Medline]
[Order article via Infotrieve]
- Yoshino S., Sasatomi E., Mori Y., Sagai M. Oral administration of lipopolysaccharide exacerbates collagen-induced arthritis in mice. J Immunol 1999; 163: 3417—3422.[Abstract/Free Full Text]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
|
