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Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

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Abstract

Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host’s response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58–60 kDa protein of LBP distinctly labeled a small population of cells located deep into the crypts. This cell population was also positive for lysozyme and α-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP together with other proteins acting in the innate immune response of the gut, such as lysozyme, defensins and intelectin.

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References

  • Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ (2000) Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1:113–118

    Article  PubMed  CAS  Google Scholar 

  • Bevins CL (2004) The Paneth cell and the innate immune response. Curr Opin Gastroenterol 20:572–580

    Article  PubMed  Google Scholar 

  • Booth AG, Kenny AJ (1974) A rapid method for the preparation of microvilli from rabbit kidney. Biochem J 142:575–581

    PubMed  CAS  Google Scholar 

  • Danielsen EM, Hansen GH (2006) Lipid raft organization and function in brush borders of epithelial cells. Mol Membr Biol 23:71–79

    Article  PubMed  CAS  Google Scholar 

  • Dann SM, Eckmann L (2007) Innate immune defenses in the intestinal tract. Curr Opin Gastroenterol 23:115–120

    Article  PubMed  CAS  Google Scholar 

  • George MD, Wehkamp J, Kays RJ, Leutenegger CM, Sabir S, Grishina I, Dandekar S, Bevins CL (2008) In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues. BMC Genomics 9:209

    Article  PubMed  Google Scholar 

  • Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, Busse LA, Zukowski MM, Wright SD (1994) Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med 179:269–277

    Article  PubMed  CAS  Google Scholar 

  • Hansen GH, Niels-Christiansen LL, Immerdal L, Hunziker W, Kenny AJ, Danielsen EM (1999) Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid Raft- and Rab17-containing compartments. Gastroenterology 116:610–622

    Article  PubMed  CAS  Google Scholar 

  • Jerala R (2007) Structural biology of the LPS recognition. Int J Med Microbiol 297:353–363

    Article  PubMed  CAS  Google Scholar 

  • Komiya T, Tanigawa Y, Hirohashi S (1998) Cloning of the novel gene intelectin, which is expressed in intestinal Paneth cells in mice. Biochem Biophys Res Commun 251:759–762

    Article  PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  • Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S (2003) Crohn’s disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 125:47–57

    Article  PubMed  CAS  Google Scholar 

  • Molmenti EP, Ziambaras T, Perlmutter DH (1993) Evidence for an acute phase response in human intestinal epithelial cells. J Biol Chem 268:14116–14124

    PubMed  CAS  Google Scholar 

  • Ogura Y, Lala S, Xin W, Smith E, Dowds TA, Chen FF, Zimmermann E, Tretiakova M, Cho JH, Hart J, Greenson JK, Keshav S, Nunez G (2003) Expression of NOD2 in Paneth cells: a possible link to Crohn’s Ileitis. Gut 52:1591–1597

    Article  PubMed  CAS  Google Scholar 

  • Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ (1990) Structure and function of lipopolysaccharide binding protein. Science 249:1429–1431

    Article  PubMed  CAS  Google Scholar 

  • Shi J (2007) Defensins and Paneth cells in inflammatory Bowel disease. Inflamm Bowel Dis 13:1284–1292

    Article  PubMed  Google Scholar 

  • Su GL, Freeswick PD, Geller DA, Wang Q, Shapiro RA, Wan YH, Billiar TR, Tweardy DJ, Simmons RL, Wang SC (1994) Molecular cloning, characterization, and tissue distribution of rat lipopolysaccharide binding protein. Evidence for extrahepatic expression. J Immunol 153:743–752

    PubMed  CAS  Google Scholar 

  • Suzuki YA, Shin K, Lonnerdal B (2001) Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry 40:15771–15779

    Article  PubMed  CAS  Google Scholar 

  • Tobias PS, Soldau K, Ulevitch RJ (1986) Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med 164:777–793

    Article  PubMed  CAS  Google Scholar 

  • Tobias PS, Soldau K, Ulevitch RJ (1989) Identification of a lipid A binding site in the acute phase reactant lipopolysaccharide binding protein. J Biol Chem 264:10867–10871

    PubMed  CAS  Google Scholar 

  • Vreugdenhil AC, Dentener MA, Snoek AM, Greve JW, Buurman WA (1999) Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response. J Immunol 163:2792–2798

    PubMed  CAS  Google Scholar 

  • Vreugdenhil AC, Snoek AM, Greve JW, Buurman WA (2000) Lipopolysaccharide-binding protein is vectorially secreted and transported by cultured intestinal epithelial cells and is present in the intestinal mucus of mice. J Immunol 165:4561–4566

    PubMed  CAS  Google Scholar 

  • Wehkamp J, Stange EF (2006) Paneth cells and the innate immune response. Curr Opin Gastroenterol 22:644–650

    Article  PubMed  Google Scholar 

  • Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H Jr, Fellermann K, Ganz T, Stange EF, Bevins CL (2005) RReduced Paneth cell alpha-defensins in ileal Crohn’s disease. Proc Natl Acad Sci USA 102:18129–18134

    Article  PubMed  CAS  Google Scholar 

  • Wershil BK, Furuta GT (2008) 4. Gastrointestinal mucosal immunity. J Allergy Clin Immunol 121:S380–S383

    Article  PubMed  CAS  Google Scholar 

  • Wrackmeyer U, Hansen GH, Seya T, Danielsen EM (2006) Intelectin: a novel lipid raft-associated protein in the enterocyte brush border. Biochemistry 45:9188–9197

    Article  PubMed  CAS  Google Scholar 

  • Zweigner J, Schumann RR, Weber JR (2006) The role of lipopolysaccharide-binding protein in modulating the innate immune response. Microbes Infect 8:946–952

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work was supported by grants from the Danish Medical Research Council and the Novo-Nordic Foundation.

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Correspondence to E. Michael Danielsen.

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Hansen, G.H., Rasmussen, K., Niels-Christiansen, LL. et al. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine. Histochem Cell Biol 131, 727–732 (2009). https://doi.org/10.1007/s00418-009-0572-6

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  • DOI: https://doi.org/10.1007/s00418-009-0572-6

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