The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.
Heparanase is an endo-β-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 co...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0127032 |
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| author | Abigail Morris Bo Wang Ida Waern Radhakrishnan Venkatasamy Clive Page Eric P Schmidt Sara Wernersson Jin-Ping Li Domenico Spina |
| author_facet | Abigail Morris Bo Wang Ida Waern Radhakrishnan Venkatasamy Clive Page Eric P Schmidt Sara Wernersson Jin-Ping Li Domenico Spina |
| author_sort | Abigail Morris |
| collection | DOAJ |
| description | Heparanase is an endo-β-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. |
| format | Article |
| id | doaj-art-0831e4fb85cb4606a600bc70f728aa60 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-0831e4fb85cb4606a600bc70f728aa602025-08-20T02:34:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012703210.1371/journal.pone.0127032The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.Abigail MorrisBo WangIda WaernRadhakrishnan VenkatasamyClive PageEric P SchmidtSara WernerssonJin-Ping LiDomenico SpinaHeparanase is an endo-β-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.https://doi.org/10.1371/journal.pone.0127032 |
| spellingShingle | Abigail Morris Bo Wang Ida Waern Radhakrishnan Venkatasamy Clive Page Eric P Schmidt Sara Wernersson Jin-Ping Li Domenico Spina The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. PLoS ONE |
| title | The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. |
| title_full | The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. |
| title_fullStr | The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. |
| title_full_unstemmed | The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. |
| title_short | The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus. |
| title_sort | role of heparanase in pulmonary cell recruitment in response to an allergic but not non allergic stimulus |
| url | https://doi.org/10.1371/journal.pone.0127032 |
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