SECRETION OF MUCUS PROTEINASE-INHIBITOR AND ELAFIN BY CLARA CELL AND TYPE-II PNEUMOCYTE CELL-LINES

The regulation of proteinases secreted by neutrophils is very importan t for the prevention of tissue injury. We recently described the isola tion of elafin from bronchial secretions, a new elastase-specific inhi bitor that is also found in the skin of patients with psoriasis. In th is study, we investigated the secretion of elafin and mucus proteinase inhibitor (MPI), another inhibitor showing sequence similarity with e lafin, in two lung carcinoma cell lines, NCI-H322 and A549, which have features of Clara cells and type II alveolar cells, respectively. The results presented show that the two inhibitors are produced when the cells are cultured either in serum-free or in serum-containing media. MPI was detected immunologically as a unique molecule of Mr 14 kD, in accordance with previous studies. Conversely, one or two elafin-immuno reactive species were detected depending on the cell line: a 12- to 14 -kD species was observed in the A549 cell line, regardless of the cult ure conditions, whereas in the NCI-H322 cell line we detected a 6-kD s pecies in serum-containing (10 % fetal calf serum) conditions and a 12 - to 14-kD species in serum-free conditions. The 12- to 14-kD molecule probably represents an active precursor of elafin. Whether the cleava ge of the 12- to 14-kD precursor giving rise to the elafin molecule is of any physiologic significance is not known. In showing for the firs t time that MPI and elafin (and its precursor) are secreted by the A54 9 cell line, this report implicates the type II alveolar cell in the d efense of the peripheral lung against the neutrophil elastase secreted during inflammation.