Am. J. Respir. Cell Mol. Biol., Vol 15, No. 2, 08 1996, 224-231.
Neutrophil transepithelial migration is dependent upon epithelial characteristics
EJ Carolan and TB Casale
University of Iowa College of Medicine, Iowa City, USA.
To better understand the mechanisms by which neutrophils migrate to the
airway lumen during an inflammatory response, we constructed an in vitro
model system to examine the interactions of human neutrophils, human lung
epithelial cells, mediators, and proinflammatory cytokines. We directly
compared neutrophil movement through three lung epithelial cell lines,
A549, H441, and 16-HBE-14o, in response to three chemoattractants, FMLP,
LTB4, and IL-8, and the proinflammatory cytokines IL-1 alpha and beta and
TNF alpha. While there was variation in the responses to the chemotaxins,
there was no correlation between the transmonolayer electrical resistance
and the ability of the neutrophils to migrate across the epithelia in
response to the agents used. FMLP, IL-8, and LTB4 induced dose- and
time-dependent neutrophil migration across all three epithelia. However,
TNF alpha- and IL-1- induced neutrophil migration occurred only through
monolayers that produced soluble chemoattractants in response to these
cytokines. Although all three epithelia produced low amounts of IL-8
constitutively, the capacity of IL-1 and TNF alpha to induce
transepithelial migration was directly associated with the ability of the
epithelia to produce large amounts of IL-8 in response to IL-1 and TNF
alpha. We conclude that the phenotype of the epithelial cell (e.g.,
capacity to produce IL-8) affects stimulated neutrophil transepithelial
migration.
