CONTRIBUTION OF SECRETORY LEUKOCYTE PROTEINASE-INHIBITOR TO THE ANTIPROTEASE DEFENSE SYSTEM OF THE PERIPHERAL LUNG - EFFECT OF OZONE-INDUCED ACUTE-INFLAMMATION

Secretory leukocyte protease inhibitor (SLPI) and elafin are structura lly similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung ravage fluid from those of alpha (1)-antitrypsin (alpha(1)-AT) that is based on the resistance of the l ow-molecular-weight antiproteases to inactivation by cetyltrimethylamm onium bromide. In a study of 23 healthy, nonsmoking volunteers, we fou nd that the low-molecular-weight antiproteases accounted for 22 +/- 2% (mean +/- SEM, n = 23) of the total neutrophil elastase-inhibitory ca pacity of human bronchoalveolar lavage fluid (BALF). Elafin activity w as below the limit of detection. SLPI activity (as measured by inhibit ion of a-chymotrypsin) accounted for 72 +/- 4% (mean +/- SEM, n = 23) of the low-molecular-weight antiprotease activity in BALF. Measurement s of SLPI in the ravage fluid samples by enzyme-linked immunosorbent a ssay (ELISA) agreed closely with values obtained by measuring the acti vity of this inhibitor. The activity of the low-molecular-weight antip roteases decreased significantly (p < 0.05), from 9.0 +/- 0.8 to 7.0 /- 0.6 pmol of neutrophil elastase inhibited per mt (mean +/- SEM, n = 23), following acute ozone exposure.