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The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus

Morris, Abigail and Wang, Bo and Waern, Ida and Venkatasamy, Radhakrishnan and Page, Clive and Schmidt, Eric P. and Wernersson, Sara and Li, Jin-Ping and Spina, Domenica (2015). The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. PloS one. 10:6, 1-15
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Official URL: http://dx.doi.org/10.1371/journal.pone.0127032

Abstract

Heparanase is an endo-a-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa(-/-)) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa(-/-) and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa(-/-) mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

Authors/Creators:Morris, Abigail and Wang, Bo and Waern, Ida and Venkatasamy, Radhakrishnan and Page, Clive and Schmidt, Eric P. and Wernersson, Sara and Li, Jin-Ping and Spina, Domenica
Title:The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus
Series/Journal:PloS one (1932-6203)
Year of publishing :2015
Volume:10
Number:6
Page range:1-15
Number of Pages:15
Publisher:Public Library of Science
ISSN:1932-6203
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X38 Human medicine, health, and safety
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
Agrovoc terms:enzymes, inflammation, hypersensitivity
Keywords:enzymes, inflammation, hypersensitivity
URN:NBN:urn:nbn:se:slu:epsilon-e-3052
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3052
Additional ID:
Type of IDID
Web of Science (WoS)000355700700047
DOI10.1371/journal.pone.0127032
ID Code:12772
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:05 Nov 2015 10:54
Metadata Last Modified:10 Feb 2016 06:31

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