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MIP-2 secreted by epithelial cells increases neutrophil and lymphocyte recruitment in the mouse intestine
  1. Y Ohtsukaa,b,
  2. J Leeb,
  3. D S Stamma,b,
  4. I R Sandersona,b
  1. aDepartment of Adult and Paediatric Gastroenterology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK, bDevelopmental Gastroenterology Laboratory, Harvard Clinical Nutrition Research Center, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
  1. Dr I R Sanderson, Department of Adult and Paediatric Gastroenterology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Suite 31, Dominion House, 59 Bartholomew Close, London EC1A 7BE, UK. i.r.sanderson{at}mds.qmw.ac.uk

Abstract

BACKGROUND Invasion of the intestinal mucosa by leucocytes is a characteristic of intestinal inflammation but the role of the epithelium in orchestrating this recruitment has not been examined in vivo. Cultured intestinal epithelial cells secrete a wide variety of chemokines, often in response to agents present in the intestinal lumen. Macrophage inflammatory protein 2 (MIP-2) is a chemokine that attracts neutrophils, and its secretion from intestinal epithelial cells is enhanced by inflammatory stimuli such as interleukin 1β. We hypothesised that the production of MIP-2 by epithelial cells would increase leucocyte migration into the intestine.

AIM To study the effects of a chemokine secreted from intestinal epithelial cells in vivo.

METHODS MIP-2 was expressed in the mouse intestinal epithelium using an epithelial cell specific promoter from the gene encoding the intestinal fatty acid binding protein. The intestines of these transgenic mice were then analysed.

RESULTS Epithelial cells from transgenic mice expressed MIP-2 but wild-type mice did not. Neutrophil recruitment, examined by myeloperoxidase (MPO) staining and total MPO activity per unit weight of intestine, was significantly increased in transgenic mice in both the small intestine and proximal colon, and this was blocked by anti-MIP-2 antibody treatment. Both intraepithelial and lamina propria lymphocytes were also increased in transgenic mice. They showed chemotactic activity to MIP-2 in the Boyden chambers and expressed MIP-2 receptor (CXCR-2) mRNA confirmed by reverse transcription-polymerase chain reaction.

CONCLUSION These experiments are the first to show a functional role for epithelial chemokines in vivo and reveal an unexpected role for the neutrophil chemokine MIP-2 in controlling mucosal lymphocyte migration.

  • chemokines
  • epithelial cells
  • intestinal mucosa
  • leucocyte recruitment
  • transgenic mouse
  • Abbreviations used in this paper

    CMF-HBSS
    Ca2+/Mg2+free Hanks' balanced salt solution
    Fabpi
    fatty acid binding protein of the intestine
    IEL
    intraepithelial lymphocyte
    IL
    interleukin
    LPL
    lamina propria lymphocyte
    LPS
    lipopolysaccharide
    MIP-2
    macrophage inflammatory protein 2
    MPO
    myeloperoxidase
    RT-PCR
    reverse transcription-polymerase chain reaction
    TCR
    T cell receptor
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  • Abbreviations used in this paper

    CMF-HBSS
    Ca2+/Mg2+free Hanks' balanced salt solution
    Fabpi
    fatty acid binding protein of the intestine
    IEL
    intraepithelial lymphocyte
    IL
    interleukin
    LPL
    lamina propria lymphocyte
    LPS
    lipopolysaccharide
    MIP-2
    macrophage inflammatory protein 2
    MPO
    myeloperoxidase
    RT-PCR
    reverse transcription-polymerase chain reaction
    TCR
    T cell receptor
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