Published ahead of print on April 10, 2003, doi:10.1165/rcmb.2003-0060OC Am. J. Respir. Cell Mol. Biol., Volume 29, Number 3, September 2003, 381-389 A more recent version of this article appeared on September 1, 2003
Submitted on February 21, 2003 House dust mite Der p 1 down-regulates defences of the lung by inactivating elastase inhibitorsAlan Brown1,1 Centre for Inflammation Research, Rayne Laboratory, Edinburgh, United Kingdom * To whom correspondence should be addressed. 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 defence mechanisms of the lung, by inactivating in vitro and ex vivo the elastase inhibitors human (h) alpha-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. Since these elastase inhibitors have antimicrobial, as well as anti-elastase activity, our results suggest that inactivation of these innate components of the lung defence system by Der p 1 may increase the susceptibility of patients with allergic inflammation to infection.
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