Epithelial Clara Cell Injury Occurs in Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

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 e...

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Bibliographic Details
Published in:American journal of transplantation 2012-11, Vol.12 (11), p.3076-3084
Main Authors: Kelly, F. L., Kennedy, V. E., Jain, R., Sindhwani, N. S., Finlen Copeland, C. A., Snyder, L. D., Eu, J. P., Meltzer, E. B., Brockway, B. L., Pavlisko, E., Stripp, B. R., Palmer, S. M.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Biomarkers - metabolism
Bronchiolitis Obliterans - etiology
Bronchiolitis Obliterans - pathology
Bronchiolitis obliterans syndrome
Bronchoalveolar Lavage Fluid - cytology
Case-Control Studies
Chronic obstructive pulmonary disease, asthma
Clara cell
Clara cell secretory protein
Epithelial Cells - metabolism
Epithelial Cells - pathology
epithelium
Female
Fluorescent Antibody Technique
Graft Rejection
Graft Survival
Humans
Immunohistochemistry
lung transplantation
Lung Transplantation - adverse effects
Lung Transplantation - methods
Lungs
Male
Medical sciences
Middle Aged
Pneumology
Prognosis
Prospective Studies
Proteins
Reference Values
Risk Factors
Severity of Illness Index
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Syndrome
Transplants & implants
Uteroglobin - genetics
Uteroglobin - metabolism
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Summary: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. The authors demonstrate that tissue transcript, tissue protein and lung fluid protein expression of Clara cell secretory protein is reduced in lung transplant recipients with bronchiolitis obliterans syndrome (BOS), suggesting that BOS involves a selective alteration in the distribution and function of bronchiolar Clara cells.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2012.04201.x