Airway epithelial cell senescence in the lung allograft.
Chronic lung allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is characterized by airway epithelial injury, impaired epithelial regeneration and subsequent airway remodeling. Increased cellular senescence has been reported in renal and liver allografts affected by chronic allograft dysfunction but the significance of cellular senescence in the airway epithelium of the transplanted lung is unknown. Thirty-four lung transplant recipients, 20 with stable graft function and 14 with BOS, underwent transbronchial lung biopsy and histochemical studies for senescence markers in small airways. Compared to nontransplant control lung tissue (n = 9), lung allografts demonstrate significantly increased airway epithelial staining for senescence-associated beta galactosidase (SA beta-gal) (p = 0.0215), p16(ink4a) (p = 0.0002) and p21(waf1/cip) (p = 0.0138) but there was no difference in expression of these markers between stable and BOS affected recipients (p > 0.05). This preliminary cross-sectional study demonstrates that cellular senescence occurs with increased frequency in the airway epithelium of the lung allograft but does not establish any association between airway epithelial senescence and BOS. A prospective longitudinal study is required to better address any potential causal association between airway epithelial senescence in stable allograft recipients and the subsequent development of BOS.
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, UK.
S M
SM
Parker
M R
MR
Goriwiec
L A
LA
Borthwick
G
G
Johnson
C
C
Ward
J L
JL
Lordan
P A
PA
Corris
G C
GC
Saretzki
A J
AJ
Fisher
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001707:Biopsy, Needle; D001989:Bronchiolitis Obliterans / Q000473:pathology* / Q000503:physiopathology; D016922:Cellular Senescence; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000502:physiology; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000473:pathology* / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D001616:beta-Galactosidase