The house dust mite allergen Der p1 catalytically inactivates alpha 1-antitrypsin by specific reactive centre loop cleavage: a mechanism that promotes airway inflammation and asthma.
Der p1, a cysteine proteinase derived from the house dust mite (HDM) Dermatophagoides pteronyssinus, is a major component of the allergic immune response in HDM atopic individuals. Recent evidence suggests that cysteine proteinase activity is important in the disease process as it 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 and inhaled via the respiratory tract. The serine proteinase inhibitor, alpha 1-antitrypsin, protects the lower respiratory tract against damage by proteinases released in the lung during inflammation. Der p1 catalytically inactivates alpha 1-antitrypsin by a thiol-dependent mechanism involving specific cleavage of the reactive centre loop and we propose that this mechanism may be important in the pathogenesis of asthma.
Kalsheker
N A
NA
Department of Clinical Laboratory Sciences, Division of Clinical Chemistry, University Hospital, Queen's Medical Centre, Nottingham, England.
Deam
S
S
Chambers
L
L
Sreedharan
S
S
Brocklehurst
K
K
Lomas
D A
DA
D000485:Allergens / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000503:physiopathology; D002384:Catalysis; D006023:Glycoproteins / Q000502:physiology*; D006868:Hydrolysis; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008925:Mites / Q000276:immunology; D008969:Molecular Sequence Data; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D000515:alpha 1-Antitrypsin