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Surfactant protein‐A protects epithelial barrier function in mice and humans during exposure to ozone
Author(s) -
Foster W. Michael,
Potts Erin N.,
Li Zhuowei,
Stiles Jane V.,
Hollingsworth John W.
Publication year - 2011
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.25.1_supplement.1036.7
Subject(s) - bronchoalveolar lavage , paracellular transport , barrier function , inflammation , chemistry , epithelium , in vivo , immunology , biology , andrology , microbiology and biotechnology , medicine , lung , pathology , permeability (electromagnetism) , biochemistry , genetics , membrane
Surfactant protein‐A (SP‐A) interacts with pulmonary and epithelial defenses. Exposure to ozone (O3), a prototypal air pollutant, leads to tissue inflammation, and loss of epithelial integrity. Following O3 exposure SP‐A levels may decrease within airway lining fluids and/or undergo structural modification, and epithelial permeability increases. To determine if SP‐A is a key component of epithelial barrier function we exposed SP‐A null, and WT mice to inhaled O3. Serum albumin levels in bronchoalveolar lavage fluid (BAL), an index of permeability, were significantly elevated at baseline and after O3 in SP‐A null as compared to WT mice. BAL serum levels correlated with epithelial permeability in vivo as evidenced by paracellular clearance of a radiomarker (492 Da, hydrophilic) assessed directly by 2‐D scintigraphy. When evaluated in humans (n=130) using a controlled laboratory exposure sensitivity to O3 was differential, with 26% of subjects exhibiting O3‐induced increases in epithelial permeability at 20 h post‐O3 as compared to filtered air. Stratified for ethnicity, Caucasian subjects with at least one copy of a minor allele of a common SP‐A polymorphism, were found to be at more than 2x the risk to sustain loss of epithelial integrity after O3, as subjects homozygous for the major, wild‐type allele. Summary these data show that functional SP‐A enhances epithelial integrity and that a common polymorphism on SP‐A 2 gene modulates risk of epithelial injury from ozone. Supported by NIH: ES016126 (JWH); AI081672 (WMF).