title: Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation.
abstract: Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow obstruction that affects a majority of lung transplant recipients and limits long-term posttransplant survival. Although epithelial injury appears central to the development of BOS, little is known regarding the specific epithelial cell types that are affected in this condition. We hypothesized that BOS would involve preferential injury to the secretory Clara cells that function in innate defense and epithelial repair. To test this hypothesis, we assessed tissue transcript, tissue protein and lung fluid protein expression of Clara cell secretory protein (CCSP), a marker for Clara cells, in lung transplant recipients with BOS, BOS-free patients and in donor controls. Our results demonstrate that CCSP tissue transcript and protein expression are significantly reduced in lung transplant recipients with BOS compared to BOS-free or donor controls. In addition, we demonstrate that CCSP protein levels are significantly reduced in the lung fluid of patients with BOS compared to BOS-free controls, in cross-sectional and longitudinal analysis. Collectively, these complementary results illustrate that BOS involves a selective alteration in the distribution and function of bronchiolar Clara cells.
authors.affiliation: Division of Pulmonary and Critical Care Medicine-Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: F L
authors.initials: FL
authors.lastname: Kelly
authors.forename: V E
authors.initials: VE
authors.lastname: Kennedy
authors.forename: R
authors.initials: R
authors.lastname: Jain
authors.forename: N S
authors.initials: NS
authors.lastname: Sindhwani
authors.forename: C A
authors.initials: CA
authors.lastname: Finlen Copeland
authors.forename: L D
authors.initials: LD
authors.lastname: Snyder
authors.forename: J P
authors.initials: JP
authors.lastname: Eu
authors.forename: E B
authors.initials: EB
authors.lastname: Meltzer
authors.forename: B L
authors.initials: BL
authors.lastname: Brockway
authors.forename: E
authors.initials: E
authors.lastname: Pavlisko
authors.forename: B R
authors.initials: BR
authors.lastname: Stripp
authors.forename: S M
authors.initials: SM
authors.lastname: Palmer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012720:Severity of Illness Index; D013577:Syndrome; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014598:Uteroglobin