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2610471 
Journal Article 
Abstract 
Mammalian chitinase family members inhibit house dust mite-induced airway hyperresponsiveness 
Inoue, Y; Dienger, K; Clark, J; Sproles, A; Lajoie, S; Lewkowich, I; Wills-Karp, M 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A5587 
English 
WOS:000208771003664 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Asthma is a chronic disease marked by airway hyperreactivity and inflammation. Although chitinase family members are induced in experimental models of asthma and in human asthmatics, their role in asthma pathogenesis remains controversial. Previously, we found that two chitinase family members, acidic mammalian chitinase (AMCase, having chitinase activity) and Ym1 (lacking chitinase activity), decreased house dust mite (HDM)-induced airway hyper-responsiveness (AHR). Interestingly, Ym1 decreased Th2 parameters, whereas AMCase did not. Based on the observation that BAL Ym1 levels in resistant mice are higher than in susceptible mice and Ym1 inhibited early processes such as Th2 cytokine production, we hypothesized that Ym1 may alter the function of antigen presenting cells (APCs) We examined its effects on the numbers, activation and antigen uptake of lung APCs. We found that rYm1 decreased the recruitment of and antigen uptake capacity of both myeloid DCs and plasmacytoid DCs. Although Ym1 did not change CCL20 production in primary murine tracheal epithelial cells, which induces immature DC migration, Ym1 significantly decreased CCL4 gene expression in lung macrophages and CCL4 production in bone marrow-derived macrophages. In summary, our results demonstrate that both AMCase and Ym1 provide protection against the development of allergen-driven AHR, but through different mechanisms. Furthermore, we demonstrate that Ym1 may provide protection against allergen-driven AHR, through suppression of DC recruitment as a result of inhibition of CCL4 production in lung macrophages, which may induce suppression of Th2 immune responses to HDM. These results suggest that modulation of this pathway may provide a novel approach for the treatment of asthma. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010