IMMUNOCYTOCHEMICAL EVIDENCE FOR EXTRACELLULAR INITIATION OF ELASTASE-INDUCED BRONCHIAL SECRETORY-CELL METAPLASIA IN HAMSTERS

The bronchus is the only region of the hamster conducting airways to d evelop secretory cell metaplasia after an intratracheal instillation o f human neutrophil elastase (HNE), We tested the hypothesis that this pathological change occurs because of cellular uptake of the enzyme th at is specific to this region. HNE, dissolved in saline, was instilled into the trachea of hamsters, that were sacrificed 5, 15, 30 or 60 mi n later for immunocytochemical localization of the enzyme, Saline-trea ted animals served as controls. By light microscopy, HNE was evident o nly in the lumen and upon the epithelial surface in all airways, at al l time points, Saline control tissues were negative, Electron microsco pic immunogold staining revealed HNE within luminal macrophages and as sociated with mucus and, to a limited extent, upon the apical cell sur face both in trachea and bronchus, A small amount of HNE staining occu rred in the intercellular space and lamina propria of bronchi, Cytopla smic gold particles were sparse both in treated and control animals, W e conclude that instilled neutrophil elastase is excluded from the epi thelial cytoplasm regardless of region. We thus reject the hypothesis of airway cellular uptake of HNE and suggest that stimulation of bronc hial secretory cells to accumulate mucin granules is initiated at the cell surface, possibly by unmasking or altering region-specific recept ors involved in signal transduction pathways governing mucin granule s ynthesis.