PROTEINASE PROTEINASE-INHIBITOR IMBALANCE IN SPUTUM SOL PHASES FROM PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE - SUGGESTIONS FOR A KEY ROLE PLAYED BY ANTILEUKOPROTEASE

In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha1-proteinase inhibitor [alpha1-PI], 2.56 muM +/- 0.53 muM and 2.39 muM +/- 0.72 muM: alpha2-macroglobulin [alpha2-MG], 0.21 muM +/- 0.07 muM and 0.16 muM +/- 0.05 muM; antileukoprotease (ALP), 1.78 muM +/- 0.57 muM and 1.53 muM +/- 0.6 muM, respectively (mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 muM +/- 0.15 muM and 0.74 muM +/- 0.15 muM for elastase-like activity [ELA], and 0.010 muM +/- 0.003 muM and 0.017 muM +/- 0.007 muM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r= -0.58; p<0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (>0.50 muM) and samples (10) with no detectable ELA (<0.18 muM). Levels of alpha1-PI and alpha2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 muM +/- 0.69 muM) than in the other group (0.58 muM +/- 0.21 muM; p<0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.