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Loss of cilia alters airway epithelial cells and evokes an immune response
Author(s) -
Gilley Sandra Kaye,
Stenbit Antine E.,
Sas Kelli M.,
Flume Patrick A.,
Bell P. Darwin
Publication year - 2010
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.24.1_supplement.612.4
Subject(s) - cilium , parenchyma , lung , biology , pathology , airway , intraflagellar transport , immune system , respiratory epithelium , immunology , microbiology and biotechnology , medicine , mutant , biochemistry , surgery , gene
Deletion of the intraflagellar transport protein, polaris, results in loss of cilia. The purpose of this study was to characterize the effects of polaris deletion on ciliated airway epithelial cells and lung parenchyma. Utilizing a conditional floxed ift88 allele under the control of the estrogen receptor, 8 cre + and 7 (control) cre − adult mice were induced with tamoxifen. Both cre + and cre − mice, at either 3 wks or 3 months post tamoxifen, appeared to be healthy. Weights were not different and lungs looked grossly normal. At both time points western blot and immunofluorescence (IF) revealed a > 80% loss of polaris in cre + lungs. Utilizing acetylated‐alpha tubulin as a marker of cilia, IF demonstrated a dramatic loss of cilia in airways from cre + mice. Interestingly, in cre + lungs, there was hypertrophy of airway epithelial cells, with increased cytoplasmic blebbing, and a decreased number of goblet cells. In BAL fluid and in lung parenchyma there was evidence of an increased inflammatory response in lungs from cre + mice and a greater number of reactive type II pneumocytes. These changes were greater at 3 months versus 3 wks in lungs from cre + mice. These results suggest that loss of cilia leads to morphologic changes of airway epithelial cells and initiates an enhanced inflammatory response in lung parenchyma. This mouse model may serve as a means for defining the role of cilia in the pathophysiology of lung injury. NIH/VA