THE HOUSE-DUST MITE ALLERGEN DER P1 CATALYTICALLY INACTIVATES ALPHA(1)-ANTITRYPSIN BY SPECIFIC REACTIVE CENTER LOOP CLEAVAGE - A MECHANISM THAT PROMOTES AIRWAY INFLAMMATION AND ASTHMA

Der p1, a cysteine proteinase derived from the house dust mite (HDM) D ermatophagoides pteronyssinus, is a major component of the allergic im mune response in HDM atopic individuals. Recent evidence suggests that cysteine proteinase activity is important in the disease process as i t increases the permeability of the allergen in the respiratory tract and disrupts the regulation of IgE synthesis. Der p1 is found in high concentrations in the faecal pellets of mites which are aerosolised an d inhaled via the respiratory tract. The serine proteinase inhibitor, alpha(1)-antitrypsin, protects the lower respiratory tract against dam age by proteinases released in the lung during inflammation. Der p1 ca talytically inactivates alpha(1)-antitrypsin by a thiol-dependent mech anism involving specific cleavage of the reactive centre loop and we p ropose that this mechanism may be important in the pathogenesis of ast hma. (C) 1996 Academic Press. Inc.