Document Detail


Endothelial and leukocyte heparan sulfates regulate the development of allergen-induced airway remodeling in a mouse model.
MedLine Citation:
PMID:  24794009     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Heparan sulfate proteoglycans (HSPGs) participate in several aspects of inflammation because of their ability to bind to growth factors, chemokines, interleukins and extracellular matrix proteins as well as promote inflammatory cell trafficking and migration. We investigated whether HSPGs play a role in the development of airway remodeling during chronic allergic asthma using mice deficient in endothelial- and leukocyte-expressed N-deacetylase/N-sulfotransferase-1 (Ndst1), an enzyme involved in modification reactions during heparan sulfate (HS) biosynthesis. Ndst1-deficient and wild type (WT) mice exposed to repetitive allergen (ovalbumin [OVA]) challenge were evaluated for the development of airway remodeling. Chronic OVA-challenged WT mice exhibited increased HS expression in the lungs along with airway eosinophilia, mucus hypersecretion, peribronchial fibrosis, increased airway epithelial thickness and smooth muscle mass. In OVA-challenged Ndst1-deficient mice, lung eosinophil and macrophage infiltration as well as airway mucus accumulation, peribronchial fibrosis and airway epithelial thickness were significantly lower than in allergen-challenged WT mice along with a trend towards decreased airway smooth muscle mass. Leukocyte and endothelial Ndst-1 deficiency also resulted in significantly decreased expression of IL-13 as well as remodeling-associated mediators such as VEGF, FGF-2 and TGF-β1 in the lung tissue. At a cellular level, exposure to eotaxin-1 failed to induce TGF-β1 expression by Ndst1-deficient eosinophils relative to WT eosinophils. These studies suggest that leukocyte and endothelial Ndst1-modified HS contribute to the development of allergen-induced airway remodeling by promoting recruitment of inflammatory cells as well as regulating expression of pro-remodeling factors such as IL-13, VEGF, TGF-β1 and FGF-2 in the lung.
Authors:
Xiao Na Ge; Sung Gil Ha; Amrita Rao; Yana G Greenberg; Muaz Nik Rushdi; Jeffrey D Esko; Savita P Rao; P Sriramarao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-2
Journal Detail:
Title:  Glycobiology     Volume:  -     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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