Several epidemiological studies suggest that exposure to house dust mite allergens plays a role in the pathogenesis of asthma. Since many of these allergens exhibit enzymatic properties, they may damage the airway epithelium.To characterize the effects of low doses of Dermatophagoides pteronyssinus on the airway epithelium, the effect of D. pteronyssinus on the epithelial bioelectric properties of tracheal fragments of non-sensitized Lewis rats was studied, using Ussing-type chamber technique.The addition of a crude D. pteronyssinus extract containing 20 mg . mL -1 of Der pI allergen in the presence of 1.5 mM dithiothreitol (DTT, an activator of cysteine proteases), induced a progressive increase in bioelectrical conductance (+ 12.01.5%, n=12, p<0.005), an index of epithelial permeability, without affecting the short circuit current (which reflects active ion transports). The D. pteronyssinus-induced increase in epithelial conductance was related to the cysteine-protease activity of the allergen since it was not observed in the absence of DTT (n=12), and was completely suppressed in the presence of 10 nM E-64, a specific inhibitor of cysteine proteases (n=12). D. pteronyssinus-induced increase in epithelial conductance could be entirely attributed to an increase in the paracellular conductance (+ 11.21.2%, n=8, p<0.01). There was no electrophysiological evidence of rupture in epithelial continuity, and no cell detachment was observed on microscopic examination.In conclusion, the cysteine protease activity of crude Dermatophagoides pteronyssinus extract is able to increase the epithelial paracellular conductance of rat tracheal tissues, even at relatively low doses that do not induce cell detachment or cell death. Eur Respir J 2000; 16: 309±315.
The aim of this study was to elucidate possible mechanisms of increased epithelial lung clearance in diffuse fibrosing alveolitis (DFA). We investigated the relationships between epithelial lung clearance as assessed by the clearance of aerosolized 99mTc-diethylene-triamine-penta-acetic acid (RC-DTPA), luminal alveolitis as assessed by bronchoalveolar lavage, and pulmonary function, in 30 nonsmokers with DFA. In 14 of these patients, RC-DTPA and lung function were determined before and during therapy with prednisolone (0.5 mg.kg-1 daily). RC-DTPA was higher in patients with DFA (4.45 +/- 2.50%.min-1) than in normal subjects (1.18 +/- 0.31%.min-1). RC-DTPA did not correlate with the number of alveolar neutrophils, but correlated positively with the number of alveolar lymphocytes, and negatively with vital capacity (VC). RC-DTPA decreased from 6.1 +/- 2.8 to 3.8 +/- 1.9%.min-1 with prednisolone. RC-DTPA before prednisolone correlated positively with the prednisolone-associated improvement in VC. We conclude that in patient with DFA, RC-DTPA is increased, and decreases but does not return to normal with corticosteroid therapy. Our data suggest that in DFA the increase in RC-DTPA could be related to the recoil-induced stretch of the respiratory epithelium and to alveolar lymphocytic inflammation.
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