Respiratory bronchiolitis-associated interstitial lung disease: a case report with bronchoalveolar lavage findings.

We report a case of respiratory bronchiolitis-associated interstitial lung disease in a young asymptomatic heavy cigarette smoker. Diagnosis was achieved by examination of specimens obtained from open lung biopsy, but retrospective evaluation of bronchoalveolar lavage findings offer some circumstantial suggestions. We provide evidence for the nature of inclusions contained in alveolar macrophages. Problems related to the classification of respiratory bronchiolitis-associated interstitial lung disease are also discussed.

Effects of MR889, a cyclic thiolic neutrophil elastase inhibitor, on rheologic properties of mucus.

MR889 is a synthetic inhibitor of human neutrophil elastase with potential in clinical conditions characterized by a high load of this proteolytic enzyme, mainly chronic obstructive pulmonary disease. On the basis of its mechanism of inhibition, it has been suggested that MR889, upon reaction with elastase, would generate new free thiol groups. The aim of this study was to investigate whether MR889, upon reaction with elastase, may modify rheologic properties, i.e. apparent viscosity and elasticity, of both human sputum and porcine stomach mucus, in ex-vivo and in vitro experiments. MR889 10(-4) M alone had no effect on rheologic properties of samples, whereas an agent with free thiol group, n-acetylcysteine 10(-4) M reduced both viscosity and elasticity. MR889 10(-4) M upon reaction with elastase 0.03 nMol (giving 83% of elastase inhibition) had no effect on rheologic properties of samples, whereas upon reaction with elastase 0.15 nMol (49% inhibition) yielded a marked decrease in viscosity. This result would suggest that MR889, in the presence of a high load of elastase, may acquire direct mucus modifying capacity, likely because of its greater utilization upon reaction with the enzyme.

Protease-antiprotease imbalance: local evaluation with bronchoalveolar lavage.

The protease-antiprotease imbalance is thought to be involved in a variety of destructive lung diseases: pulmonary emphysema, chronic bronchitis, cystic fibrosis and adult respiratory distress syndrome. Bronchoalveolar lavage allowed the investigators to assess the protease-antiprotease shift in such conditions but sometimes gave conflicting results. The role of bronchoalveolar lavage as a research and diagnostic tool in diseases characterised by protease-antiprotease imbalance is reviewed, as well as its potential usefulness in the near future.

Some properties of the alkaline proteinase from Aspergillus melleus.

Seaprose is a semi-alkaline proteinase produced by Aspergillus melleus. The aim of our study was to further characterize the properties of this enzyme, particularly looking at its interaction with alpha 1-proteinase inhibitor, the major human plasma proteinase inhibitor. We studied the cleavage of three synthetic peptide substrates induced by seaprose and the inhibitory profile of the enzyme by means of a panel of inhibitors, including alpha 1-proteinase inhibitor. The interaction between seaprose and alpha 1-proteinase inhibitor was also studied with SDS-PAGE. Finally, the elastolytic activity of seaprose was checked by means of bovine elastin solubilization. We found that seaprose cleaves preferentially the substrate containing a Phe residue in the P1 position. The inhibitory profile showed that seaprose is a serine-proteinase that cannot be inhibited by alpha 1-proteinase inhibitor. The SDS-PAGE revealed that alpha 1-proteinase inhibitor, after incubation with seaprose, underwent a limited proteolysis. Finally, seaprose 10(-2) M and 10(-3) M was able to solubilize bovine elastin. We conclude that seaprose is a serine-proteinase able to inactivate human alpha 1-proteinase inhibitor with limited proteolysis at (or near) the active site and that it has mild elastinolytic capacity.