INACTIVATION OF ALPHA-1-PROTEINASE INHIBITOR BY ALVEOLAR INFLAMMATORYCELLS FROM SMOKING PATIENTS WITH OR WITHOUT EMPHYSEMA

The aim of this study was to evaluate the ability of alveolar inflamma tory cells recovered by bronchoalveolar lavage from the lower respirat ory tract of 17 smoking patients with or without emphysema to inactiva te alpha1-proteinase inhibitor (alpha1-PI). The presence of emphysema was determined and quantified using CT scan and was evidenced in 8 pat ients (Group 1), whereas 9 patients exhibited a normal CT scan (Group 2). Patients with emphysema had lower values of FEV1, DL(CO), and rest ing PO2 and higher values of RV/TLC ratio than patients without emphys ema. BAL analysis showed a higher percentage of neutrophils and of mye loperoxidase (MPO) in BAL fluid in Group 1 than in Group 2. Alveolar i nflammatory cells stimulated or not with phorbol myristate acetate (PM A) were incubated for 45 min with purified alpha1-PI, and the results were expressed as a percentage of inactivation of alpha1-PI as evaluat ed by its inhibitory activity against porcine pancreatic elastase or h uman neutrophil elastase. In Group 2, unstimulated alveolar inflammato ry cells inactivated only 3.3 +/- 0.7% alpha1-PI and stimulated cells inactivated only 5.4 +/- 1.1% alpha1-PI. In marked contrast, in Group 1, a significant loss of the antielastase function of alpha1-PI was ob served (p < 0.001) when alpha1-PI was incubated with unstimulated cell s (24.2 +/- 8.9%) or stimulated cells (35 +/- 8.9%) from Group 1. The addition of catalase to the cell suspension was associated with a sign ificant decrease in the inactivation of alpha1-PI (from 35 +/- 8.9 to 10.2 +/- 1.2%, Group 1). Inactivation of alpha1-PI by activated cells was dramatically increased by the addition of MPO (25 mU/ml) (Group 1, 85.2 +/- 3.2%; Group 2, 79.1 +/- 4.3%). A close relationship was obse rved between the emphysema score and the ability of cells to inactivat e alpha1-PI (r = 0.8, p < 0.001). Our results demonstrate that alveola r inflammatory cells from smoking patients with emphysema have the abi lity to inactivate alpha1-PI spontaneously, whereas cells from smokers without detectable emphysema do not. These results suggest that the e mphysema observed in some smokers is related to the development of an ongoing inflammation in peripheral airways, in which activated neutrop hils may play a pivotal role in the progressive destruction of lung pa renchyma through alpha1-PI inactivation.