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Lung epithelial cells downmodulate neutrophil‐endothelial interactions in response to inflammatory stimuli
Author(s) -
Weppler Amy Lynn,
Issekutz Andrew C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a649-a
Subject(s) - endothelium , umbilical vein , tumor necrosis factor alpha , inflammation , microbiology and biotechnology , epithelium , barrier function , a549 cell , endothelial stem cell , chemistry , interleukin 8 , immunology , respiratory epithelium , alveolar epithelium , adhesion , lung , cytokine , in vitro , biology , medicine , pathology , biochemistry , endocrinology , organic chemistry
Endothelial cells (EC) are in close proximity to epithelial cells (EpC) in the lung. To mimic this in vitro , we established a bilayer culture model on Transwell filters to examine the interactions between EC and lung EpC during leukocyte adhesion/transendothelial migration. Human umbilical vein EC (HUVEC) were seeded on one surface of a filter with 0.4 μm pores, and alveolar epithelial‐derived A549 cells were seeded on the other side of the same filter. Using various stimuli, including interleukin‐1 (IL‐1), tumor necrosis factor‐α (TNF‐α), and killed E. coli, human neutrophil adhesion and transendothelial migration was diminished when HUVEC were grown adjacent to lung EpC compared with when grown alone. This was observed regardless of whether the endothelium was activated apically or basolaterally. Similarly, E‐selectin upregulation on endothelium grown in bilayers was significantly less than that of endothelium grown alone with the same stimuli as above. However, these differences were more pronounced when the endothelium was activated basolaterally, suggesting that the epithelium mediates its protective effects both through its function as a physical barrier and via yet to be defined mechanisms. At high concentrations of cytokines, these differences were abrogated, suggesting that the epithelium loses its protective effect under conditions of intense inflammation. These findings indicate that lung EpC may be protective or may downmodulate endothelial activation for neutrophil recruitment during pulmonary inflammation and this protection is mediated by barrier‐dependent and barrier‐independent mechanisms. Supported by NSHRF, IWK Health Centre and CIHR