THE ELASTASE-INDUCED EXPRESSION OF SECRETORY LEUKOCYTE PROTEASE INHIBITOR IS DECREASED IN REMODELED AIRWAY EPITHELIUM

During airway inflammation, proteinases such as human leukocyte elasta se are actively secreted. Secretory leukocyte protease inhibitor is a major serine proteinase inhibitor, secreted by bronchial, bronchiolar and lung epithelial cells. We recently identified secretory leukocyte protease inhibitor in human nasal epithelium, exclusively in remodelle d areas of the surface epithelium. We now investigated the influence o f remodelling and inflammation of the nasal tissue on the in vitro cap acity of these cells to respond to human leukocyte elastase. Primary c ultures of surface epithelial cells were established from various nasa l polyp samples. At confluency, cell cultures were exposed to differen t human leukocyte elastase concentrations. The secretory leukocyte pro tease inhibitor immunocytolocalization, expression and secretion were then investigated. Immunocytochemistry, showed a human leukocyte elast ase dose-dependent increase of secretory leukocyte protease inhibitor containing cells and a basal extracellular localization of secretory l eukocyte protease inhibitor after incubation with 100 mu g/ml human le ukocyte elastase. The relative amount of secretory leukocyte protease inhibitor mRNA transcripts increased with respect to the human leukocy te elastase concentration. Nevertheless, the potential stimulation of secretory leukocyte protease inhibitor secretion by human leukocyte el astase was lower in the more remodelled and inflamed tissue. Our resul ts suggest that the contribution of the surface epithelial cells of po orly remodelled tissues to the protection against the deleterious effe ct of neutrophil proteinases is severely decreased in highly remodelle d and inflamed tissues. (C) 1997 Elsevier Science B.V.