Am. J. Respir. Cell Mol. Biol., Vol 17, No. 6, Dec 1997, 727-732.
Cytokine-induced neutrophil transepithelial migration is dependent upon epithelial orientation
EJ Carolan, DA Mower and TB Casale
Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, USA.
The mechanisms by which mediators and cytokines stimulate neutrophils to
migrate across the lung epithelium are still unclear. We hypothesized that
neutrophil transepithelial migration depends upon polarity of the
epithelium. We therefore compared neutrophil migration through human lung
Type II-like alveolar epithelial cell line (A549) monolayers grown on the
upper versus lower surface of permeable filters to simulate apical-to-basal
and basal-to-apical movement of neutrophils, respectively. The classic
chemoattractants formyl- methionylleucylphenylalanine (FMLP), leukotriene
B4 (LTB4), and interleukin-8 (IL-8) induced equivalent neutrophil
transepithelial migration in the apical-to-basal and basal-to-apical
directions. However, the degree of neutrophil transepithelial migration was
significantly greater in the basal-to-apical direction in response to
either IL-1beta or tumor necrosis factor-alpha (TNF-alpha). Enhanced
TNF-alpha-induced neutrophil migration through A549 monolayers in the
basal-to-apical direction occurred regardless of whether the TNF-alpha was
above or below the filter/monolayer complex. Actinomycin D pretreatment of
A549 monolayers had no effect on FMLP-induced neutrophil transepithelial
migration, but markedly (about 75%) inhibited both TNF-alpha- and
IL-1beta-induced neutrophil transepithelial migration, regardless of
monolayer orientation. Thus, in contrast to classic chemoattractants,
IL-1beta and TNF-alpha induced greater neutrophil transepithelial migration
in a basal-to-apical direction, and this occurred independently of the
cytokine location, but depended upon intact metabolic capacity of the A549
cells. These data suggest that the mechanisms important for neutrophil
transepithelial migration in response to classic chemoattractants differ
from those important for migration in response to inflammatory cytokines.
