Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation

DOI Web Site Web Site 被引用文献4件
  • Ivan K. H. Poon
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Katharine J. Goodall
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Simon Phipps
    School of Biomedical Sciences University of Queensland, Brisbane Australia
  • Jenny D. Y. Chow
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Eloisa B. Pagler
    The John Curtin School of Medical Research Australian National University Canberra Australia
  • Daniel M. Andrews
    Cancer Immunology Program Peter MacCallum Cancer Centre East Melbourne Australia
  • Carly L. Conlan
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Gemma F. Ryan
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Julie A. White
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Michael K. L. Wong
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia
  • Catherine Horan
    The John Curtin School of Medical Research Australian National University Canberra Australia
  • Klaus I. Matthaei
    The John Curtin School of Medical Research Australian National University Canberra Australia
  • Mark J. Smyth
    QIMR Berghofer Medical Research Institute Royal Brisbane Hospital Herston Australia
  • Mark D. Hulett
    Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Australia

書誌事項

公開日
2014-02-14
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/eji.201343645
公開者
Wiley

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説明

<jats:p>Heparanase is a β‐<jats:sc>d</jats:sc>‐endoglucuronidase that cleaves heparan sulphate, a key component of the ECM and basement membrane. The remodelling of the ECM by heparanase has been proposed to regulate both normal physiological and pathological processes, including wound healing, inflammation, tumour angiogenesis and cell migration. Heparanase is also known to exhibit non‐enzymatic functions by regulating cell adhesion, cell signalling and differentiation. In this study, constitutive heparanase‐deficient (Hpse<jats:sup>−/−</jats:sup>) mice were generated on a C57BL/6 background using the Cre/loxP recombination system, with a complete lack of heparanase mRNA, protein and activity. Although heparanase has been implicated in embryogenesis and development, Hpse<jats:sup>−/−</jats:sup> mice are anatomically normal and fertile. Interestingly, consistent with the suggested function of heparanase in cell migration, the trafficking of dendritic cells from the skin to the draining lymph nodes was markedly reduced in Hpse<jats:sup>−/−</jats:sup> mice. Furthermore, the ability of Hpse<jats:sup>−/−</jats:sup> mice to generate an allergic inflammatory response in the airways, a process that requires dendritic cell migration, was also impaired. These findings establish an important role for heparanase in immunity and identify the enzyme as a potential target for regulation of an immune response.</jats:p>

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