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

Poon, Ivan K. H., Goodall, Katharine J., Phipps, Simon, Chow, Jenny D. Y., Pagler, Eloisa B., Andrews, Daniel M., Conlan, Carly L., Ryan, Gemma F., White, Julie A., Wong, Michael K. L., Horan, Catherine, Matthaei, Klaus I., Smyth, Mark J. and Hulett, Mark D. (2014) Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation. European Journal of Immunology, 44 4: 1016-1030. doi:10.1002/eji.201343645


Author Poon, Ivan K. H.
Goodall, Katharine J.
Phipps, Simon
Chow, Jenny D. Y.
Pagler, Eloisa B.
Andrews, Daniel M.
Conlan, Carly L.
Ryan, Gemma F.
White, Julie A.
Wong, Michael K. L.
Horan, Catherine
Matthaei, Klaus I.
Smyth, Mark J.
Hulett, Mark D.
Title Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 1521-4141
0014-2980
Publication date 2014-04-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/eji.201343645
Open Access Status Not Open Access
Volume 44
Issue 4
Start page 1016
End page 1030
Total pages 15
Place of publication Weinheim, Germany
Publisher Wiley-VCH
Language eng
Formatted abstract
Heparanase is a β-d-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−/−) 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−/− 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−/− mice. Furthermore, the ability of Hpse−/− 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.
Keyword Allergy
DC
Heparanase
Inflammation
Migration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
School of Medicine Publications
 
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