The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation
- 1Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands
- 2James Hogg Research Centre, Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, St Paul's Hospital, Vancouver, Canada
- Correspondence to Professor A J M van Oosterhout, Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University Medical Center Groningen (UMCG), Hanzeplein 1, NL-9713GZ Groningen, The Netherlands;
Contributors SP performed the cell studies, mouse experiments, analysed and interpreted the data and wrote the manuscript. MN designed and supervised the mouse experiments and edited the manuscript. TH interpreted the IHC data and contributed to the manuscript discussion. MB performed the HDM-IgE ELISA. RG assisted on the Flexivent and ear swelling experiment. AO supervised and edited the manuscript. IH coordinated and designed the studies, supervised the cell experiments and edited the manuscript.
- Received 11 June 2011
- Accepted 21 November 2011
- Published Online First 13 December 2011
Background House dust mite (HDM) allergens have been reported to increase airway epithelial permeability, thereby facilitating access of allergens and allergic sensitisation.
Objectives The authors aimed to understand which biochemical properties of HDM are critical for epithelial immune and barrier responses as well as T helper 2-driven experimental asthma in vivo.
Methods Three commercially available HDM extracts were analysed for endotoxin levels, protease and chitinase activities and effects on transepithelial resistance, junctional proteins and pro-inflammatory cytokine release in the bronchial epithelial cell line 16HBE and normal human bronchial cells. Furthermore, the effects on epithelial remodelling and airway inflammation were investigated in a mouse model.
Results The different HDM extracts varied extensively in their biochemical properties and induced divergent responses in vitro and in vivo. Importantly, the Greer extract, with the lowest serine protease activity, induced the most pronounced effects on epithelial barrier function and CCL20 release in vitro. In vivo, this extract induced the most profound epithelial E-cadherin delocalisation and increase in CCL20, CCL17 and interleukin 5 levels, accompanied by the most pronounced induction of HDM-specific IgE, goblet cell hyperplasia, eosinophilic inflammation and airway hyper-reactivity.
Conclusions This study shows the ability of HDM extracts to alter epithelial immune and barrier responses is related to allergic sensitisation but independent of serine/cysteine protease activity.
- bronchial epithelium
- Th2-mediated inflammation and asthma
- airway epithelium
- allergic lung disease
- asthma genetics
- asthma mechanisms
- COPD mechanisms
- innate immunity
- lymphocyte biology
- COPD exacerbations
S Post and M C Nawijn contributed equally to the manuscript.
A J M van Oosterhout and I H Heijink share senior authorship.
Funding This study was supported by a grant from the Netherlands Asthma Foundation (NAF 3.2.07.019).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.