Tg. Christensen et Pa. Alonso, IMMUNOCYTOCHEMICAL EVIDENCE FOR EXTRACELLULAR INITIATION OF ELASTASE-INDUCED BRONCHIAL SECRETORY-CELL METAPLASIA IN HAMSTERS, The European respiratory journal, 9(3), 1996, pp. 535-541
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.