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2626755 
Journal Article 
Abstract 
Different biochemical properties of house dust mite induce divergent epithelial and inflammatory responses 
Post, S; Nawijn, M; van Oosterhout, A; Heijink, IH 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1444 
English 
WOS:000208771000445 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Exposure to house dust mite (HDM) is an important cause of allergic asthma, leading to allergic sensitization when its transepithelial delivery is facilitated by disruption of the epithelial barrier. Since it is unknown which component or biochemical activity in HDM is critical for allergic sensitization, we aimed to investigate the effects of HDM on the pro-inflammatory phenotype of the airway epithelium in vitro and in vivo.

Methods: We analyzed extracts from four different HDM preparations for their proteolytic activity, chitinase activity and endotoxin content. Furthermore, we tested the effects of these HDM extracts on epithelial barrier function and cytokine/chemokine release in vitro in human bronchial epithelial cells (16HBE). In addition, we evaluated the in vivo effects of intratracheal delivery of the HDM extracts on the airway epithelium and the induction of an inflammatory response in BALB/c mice.

Results: The protease activities varied significantly between the different HDM preparations. In two of the HDM extracts we mainly detected serine protease activity, which induced epithelial detachment upon prolonged exposure in vitro (4-24 hrs). The other extracts revealed chitinase activity and protease activity different from serine or cysteine. Exposure of 16HBE cells to HDM extracts in vitro induced different effects on barrier function. Here, three HDM extracts induced a transient decrease in epithelial resistance and delocalization of junctional proteins (e.g. ZO-1 and E-cadherin). This was independent of serine or cysteine proteases, linking these effects to other (proteolytic) activities or pattern recognition pathways. Although all extracts low levels of GM-CSF, only one extract induced substantial production of CCL20, a chemokine that recruits immature dendritic cells and T-lymphocytes. Interestingly, the latter extract also caused profound epithelial E-cadherin delocalization, goblet cell hyperplasia and cellular inflammation in vivo, while the other extracts only induced mild effects in vivo. Endotoxin levels and chitinase activities were not related to the observed biological effects of HDM extracts in vitro and in vivo.

Conclusions: Our results show that the biochemical activities vary extensively among different HDM preparations. Remarkably, transient defects in epithelial barrier function and induction of pro-inflammatory cytokines (e.g. CCL20) in vitro are unrelated to cysteine/serine protease or chitinase activity present in the HDM preparation. Similarly, the induction of airway inflammation and epithelial remodeling in vivo were not related to the enzymatic activities of the HDM extracts. Therefore, these results indicate that other, yet unidentified, components in the extracts play a role in the innate immune response to HDM. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010