Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition

Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush–border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients.

[1]  Kyle R. Eberlin,et al.  A novel model of acute murine hindlimb ischemia. , 2006, American journal of physiology. Heart and circulatory physiology.

[2]  R. Hodin,et al.  The Pro-inflammatory Cytokines, IL-1β and TNF-α, Inhibit Intestinal Alkaline Phosphatase Gene Expression , 2006 .

[3]  A. Waheed,et al.  Proteomic characterization of lipid rafts markers from the rat intestinal brush border. , 2006, Biochemical and Biophysical Research Communications - BBRC.

[4]  D. Meijer,et al.  On the role and fate of LPS-dephosphorylating activity in the rat liver. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[5]  L. Magnotti,et al.  Burns, bacterial translocation, gut barrier function, and failure. , 2005, The Journal of burn care & rehabilitation.

[6]  I. Autenrieth,et al.  Intestinal epithelial barrier and mucosal immunity , 2005, Cellular and Molecular Life Sciences.

[7]  I. Autenrieth,et al.  Intestinal epithelial barrier and mucosal immunity , 2005, Cellular and Molecular Life Sciences.

[8]  M. Fink,et al.  Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level. , 2005, Critical care clinics.

[9]  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.

[10]  R. Gamelli,et al.  Role of the gastrointestinal tract in burn sepsis. , 2005, The Journal of burn care & rehabilitation.

[11]  H. Hechtman,et al.  Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Millán,et al.  Accelerated Fat Absorption in Intestinal Alkaline Phosphatase Knockout Mice , 2003, Molecular and Cellular Biology.

[13]  W. Seinen,et al.  Calf Intestinal Alkaline Phosphatase, a Novel Therapeutic Drug for Lipopolysaccharide (LPS)-Mediated Diseases, Attenuates LPS Toxicity in Mice and Piglets , 2003, Journal of Pharmacology and Experimental Therapeutics.

[14]  D. Alpers,et al.  Rat enterocytes secrete SLPs containing alkaline phosphatase and cubilin in response to corn oil feeding. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[15]  M. Fink Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness , 2003, Current opinion in critical care.

[16]  B. Hinnebusch,et al.  Enterocyte response to ischemia is dependent on differentiation state , 2001, Journal of Gastrointestinal Surgery.

[17]  C. Nagler‐Anderson Man the barrier! strategic defences in the intestinal mucosa , 2001, Nature Reviews Immunology.

[18]  F. Moore,et al.  POST‐INJURY MULTIPLE ORGAN FAILURE: THE ROLE OF THE GUT , 2001, Shock.

[19]  R. Lorenz,et al.  The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota , 2001, Cellular microbiology.

[20]  D. Hollander Intestinal permeability, leaky gut, and intestinal disorders , 1999, Current Gastroenterology Reports.

[21]  D. Brenner,et al.  Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. , 1999, Journal of immunology.

[22]  M. Weiser,et al.  Intestinal reperfusion injury is mediated by IgM and complement. , 1999, Journal of applied physiology.

[23]  D. Brenner,et al.  Curcumin Blocks Cytokine-Mediated NF-κB Activation and Proinflammatory Gene Expression by Inhibiting Inhibitory Factor I-κB Kinase Activity , 1999, The Journal of Immunology.

[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]  V. Rudick,et al.  Gut decontamination reduces bowel ischemia-induced lung injury in rats. , 1997, Chest.

[26]  S. Meng,et al.  Cellular growth state differentially regulates enterocyte gene expression in butyrate-treated HT-29 cells. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[27]  L. Gianotti,et al.  Nutritional Support to Prevent and Treat Multiple Organ Failure , 1996, World Journal of Surgery.

[28]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[29]  J. Gornbein,et al.  Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. , 1995, JPEN. Journal of parenteral and enteral nutrition.

[30]  S. Meng,et al.  Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state. , 1995, The American journal of physiology.

[31]  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.

[32]  M. Engle,et al.  The secretion of intestinal alkaline phosphatase (IAP) from the enterocyte. , 1994, Journal of gastroenterology.

[33]  S. Meng,et al.  Temporal pattern of rat small intestinal gene expression with refeeding. , 1994, The American journal of physiology.

[34]  J. Marshall,et al.  The Gastrointestinal Tract The “Undrained Abscess” of Multiple Organ Failure , 1993, Annals of surgery.

[35]  F. Cerra,et al.  Multiple organ failure syndrome. , 1990, Disease-a-month : DM.

[36]  A. Baykov,et al.  A malachite green procedure for orthophosphate determination and its use in alkaline phosphatase-based enzyme immunoassay. , 1988, Analytical biochemistry.

[37]  R J Smith,et al.  The gut: a central organ after surgical stress. , 1988, Surgery.

[38]  C. Slaughter,et al.  Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Moore,et al.  Benefits of immediate jejunostomy feeding after major abdominal trauma--a prospective, randomized study. , 1986, The Journal of trauma.

[40]  H. Harris,et al.  Evolution of alkaline phosphatases in primates. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[41]  B Eiseman,et al.  Multiple organ failure. , 1977, Surgery, gynecology & obstetrics.

[42]  H. Scott,et al.  Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. , 1970, Archives of surgery.