On the role and fate of LPS-dephosphorylating activity in the rat liver.

Gut-derived lipopolysaccharide (LPS) plays a role in the pathogenesis of liver diseases like fibrosis. The enzyme alkaline phosphatase (AP) is present in, among others, the intestinal wall and liver and has been previously shown to dephosphorylate LPS. Therefore, we investigated the effect of LPS on hepatic AP expression and the effect of AP on LPS-induced hepatocyte responses. LPS-dephosphorylating activity was expressed at the hepatocyte canalicular membrane in normal and fibrotic animals. In addition to this, fibrotic animals also displayed high LPS-dephosphorylating activity around bile ducts. The enzyme was shown to dephosphorylate LPS from several bacterial species. LPS itself rapidly enhanced the intrahepatic mRNA levels for this enzyme within 2 h by a factor of seven. Furthermore, in vitro and in vivo studies showed that exogenous intestinal AP quickly bound to the asialoglycoprotein receptor on hepatocytes. This intestinal isoform significantly attenuated LPS-induced hepatic tumor necrosis factor-alpha and nitric oxide (nitrite and nitrate) responses in vitro. The enzyme also reduced LPS-induced hepatic glycogenolysis in vivo. This study shows that LPS enhances AP expression in hepatocytes and that intestinal AP is rapidly taken up by these same cells, leading to an attenuation of LPS-induced responses in vivo. Gut-derived LPS-dephosphorylating activity or enzyme upregulation within hepatocytes by LPS may therefore be a protective mechanism within the liver.

[1]  M. Matthay,et al.  Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock. , 2004, Blood.

[2]  J. Kline,et al.  Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[3]  S. Chien,et al.  Parenteral sesame oil attenuates oxidative stress after endotoxin intoxication in rats. , 2004, Toxicology.

[4]  E. Arias,et al.  Deaths: final data for 2001. , 2003, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[5]  E. Giamarellos‐Bourboulis,et al.  Systemic endotoxaemia following obstructive jaundice: the role of lactulose. , 2003, The Journal of surgical research.

[6]  Christian Jobin,et al.  Toll‐Like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells , 2003, Hepatology.

[7]  J. Marshall,et al.  Such stuff as dreams are made on: mediator-directed therapy in sepsis , 2003, Nature Reviews Drug Discovery.

[8]  J. Udagawa,et al.  Strategic Compartmentalization of Toll-Like Receptor 4 in the Mouse Gut1 , 2003, The Journal of Immunology.

[9]  D. Meijer,et al.  Removal of Phosphate from Lipid A as a Strategy to Detoxify Lipopolysaccharide , 2002, Shock.

[10]  H. Tilg,et al.  Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting. , 2002, Liver.

[11]  H. Seguchi,et al.  Lipopolysaccharide administration increases acid and alkaline phosphatase reactivity in the cardiac muscle , 2002, Microscopy research and technique.

[12]  T. Matsunaga,et al.  Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. , 2002, Clinical Biochemistry.

[13]  D. Golenbock,et al.  Innate immune recognition of lipopolysaccharide by endothelial cells , 2002, Critical care medicine.

[14]  A. Sozinov Systemic Endotoxemia during Chronic Viral Hepatitis , 2002, Bulletin of Experimental Biology and Medicine.

[15]  R. Tompkins,et al.  Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance. , 2002, American journal of physiology. Endocrinology and metabolism.

[16]  C. Lionis,et al.  In what extent anemia coexists with cognitive impairment in elderly: a cross-sectional study in Greece , 2001, BMC family practice.

[17]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[18]  A. Aderem,et al.  Toll-like receptors in the induction of the innate immune response , 2000, Nature.

[19]  G. Su,et al.  CD14 expression and production by human hepatocytes. , 1999, Journal of hepatology.

[20]  Yoshinori Nagai,et al.  MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4 , 1999, The Journal of experimental medicine.

[21]  S. Sheen-Chen,et al.  Obstructive jaundice alters Kupffer cell function independent of bacterial translocation. , 1998, The Journal of surgical research.

[22]  D. Rockey,et al.  Chylomicrons alter the hepatic distribution and cellular response to endotoxin in rats , 1998, Hepatology.

[23]  Y. Takeyama,et al.  Impaired Transport of Lipopolysaccharide Across the Hepatocytes in Rats with Cerulein‐Induced Experimental Pancreatitis , 1998, Pancreas.

[24]  M. Ali,et al.  Elimination of alkaline phosphatases from circulation by the galactose receptor. Different isoforms are cleared at various rates. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[25]  D. Meijer,et al.  Dephosphorylation of endotoxin by alkaline phosphatase in vivo. , 1997, The American journal of pathology.

[26]  J. Kuiper,et al.  Human recombinant apolipoprotein E redirects lipopolysaccharide from Kupffer cells to liver parenchymal cells in rats In vivo. , 1997, The Journal of clinical investigation.

[27]  D. Meijer,et al.  A physiologic function for alkaline phosphatase: endotoxin detoxification. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[28]  P. Detmers,et al.  Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase. , 1995, Journal of immunology.

[29]  D. Ahnen,et al.  Synthesis and parallel secretion of rat intestinal alkaline phosphatase and a surfactant-like particle protein. , 1995, The American journal of physiology.

[30]  J. Thomas-Oates,et al.  Preparation and structural analysis of oligosaccharide monophosphates obtained from the lipopolysaccharide of recombinant strains of Salmonella minnesota and Escherichia coli expressing the genus-specific epitope of Chlamydia lipopolysaccharide. , 1994, European journal of biochemistry.

[31]  C. M. Colley,et al.  Multicomponent analysis for alkaline phosphatase isoenzyme determination by multiple linear regression. , 1994, Clinical chemistry.

[32]  T. Kirikae,et al.  Bacterial endotoxin: molecular relationships of structure to activity and function , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  H. Northoff,et al.  Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I , 1993, Infection and immunity.

[34]  H. Harris,et al.  Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. , 1993, The Journal of clinical investigation.

[35]  M. Järvinen,et al.  A comparative study of methods for demonstration and quantification of capillaries in skeletal muscle. , 1993, Acta histochemica.

[36]  S. Treon,et al.  Lipopolysaccharide (LPS) Processing by Kupffer Cells Releases a Modified LPS with Increased Hepatocyte Binding and Decreased Tumor Necrosis Factor-α Stimulatory Capacity , 1993, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[37]  M. Kaplan,et al.  Clinical use of serum enzymes in liver disease , 1988, Digestive Diseases and Sciences.

[38]  S. Goyert,et al.  The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. , 1988, Journal of immunology.

[39]  E. McGroarty,et al.  High-molecular-weight components in lipopolysaccharides of Salmonella typhimurium, Salmonella minnesota, and Escherichia coli , 1985, Journal of bacteriology.

[40]  J. Wiggins,et al.  Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities , 1984, Infection and immunity.

[41]  D. Meijer,et al.  The role of the liver in clearance of glycoproteins from the general circulation, with special reference to intestinal alkaline phosphatase , 1982, Pharmaceutisch Weekblad.

[42]  E. Wisse,et al.  Uptake by liver cells of endotoxin following its intravenous injection. , 1981, Laboratory investigation; a journal of technical methods and pathology.

[43]  A. Reddi,et al.  Collagenous bone matrix-induced endochondral ossification hemopoiesis , 1976, The Journal of cell biology.

[44]  A. Novikoff,et al.  ENZYME LOCALIZATIONS WITH WACHSTEIN-MEISEL PROCEDURES: REAL OR ARTIFACT , 1967, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[45]  D. Eslin,et al.  From bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 23, 2013. For personal use only. , 2002 .

[46]  P. Olinga,et al.  Effect of human liver source on the functionality of isolated hepatocytes and liver slices. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[47]  A. Fontanilles,et al.  Characterization of alkaline phosphatase in polymorphonuclear neutrophils from normal sheep. , 1988, Enzyme.

[48]  H. McClure,et al.  The Digestive System , 1978 .

[49]  H. Janowitz Digestive system. , 1961, Annual review of physiology.