This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0060OCv1 29/3/381    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brown, A. Articles by Sallenave, J.-M. Search for Related Content PubMed PubMed Citation Articles by Brown, A. Articles by Sallenave, J.-M.

House Dust Mite Der p 1 Downregulates Defenses of the Lung by Inactivating Elastase Inhibitors

School of Pharmaceutical Sciences, Boots Building, University of Nottingham, Nottingham; Rayne Laboratory, MRC Centre for Inflammation Research, Edinburgh University Medical School, Edinburgh; and Division of Clinical Chemistry, Queens Medical Centre, University Hospital, Nottingham, United Kingdom

Address correspondence to: J.-M. Sallenave, Rayne Laboratory, MRC Centre for Inflammation Research, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, UK. E-mail: jsallenave{at}srv1.med.ed.ac.uk

House dust mites (HDM) are the most common source of aeroallergens and in genetic susceptible individuals can cause symptoms ranging from atopic dermatitis to bronchial asthma. Der p 1, a major target of the human immune responses to HDM, through its enzymatic properties can modulate the adaptive immune system by the cleavage of CD23 and CD25. The consequences of this would be to promote allergic inflammatory responses. Furthermore, by disrupting epithelial tight junctions Der p 1 facilitates the transport of allergen across the epithelium. Here, we report that Der p 1 has additional effects on the innate defense mechanisms of the lung, by inactivating in vitro and ex vivo the elastase inhibitors human (h) 1-proteinase inhibitor (h-A1-Pi), mouse (m-), (but not human [h])-SLPI and h-elafin. We confirm that Der p 1 contain both cysteine and serine proteinases, and extend this finding to demonstrate for the first time that h-elafin is particularly sensitive to the biological activity of the latter. Because these elastase inhibitors have antimicrobial, as well as antielastase activity, our results suggest that inactivation of these innate components of the lung defense system by Der p 1 may increase the susceptibility of patients with allergic inflammation to infection.

Abbreviations: 1-proteinase inhibitor, A1-Pi • acute respiratory distress syndrome, ARDS • bronchoalveolar lavage fluid, BALF • dimethyl sulfoxide, DMSO • dithiothreitol, DTT • house dust mite, HDM • human neutrophil elastase, HNE • interleukin, IL • polyacrylamide gel electrophoresis, PAGE • phosphate-buffered saline, PBS • soybean trypsin inhibitor, SBTI • secretory leukocyte protease inhibitor, SLPI