Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis.
Abnormal apoptotic mechanisms are associated with disease pathogenesis. Because the asthmatic bronchial epithelium is characteristically damaged with loss of columnar epithelial cells, we postulated that this is due to unscheduled apoptosis. Using an antibody directed toward the caspase cleavage product of poly(ADP-ribose) polymerase, immunohistochemistry applied to endobronchial biopsies showed higher levels of staining in the bronchial epithelium of subjects with asthma as compared with normal control subjects (% epithelial staining [median (range) = 10.5 (1.4-24.5) versus 0.4 (0.0-9.7)]; P < 0.001). Because we were unable to determine whether this difference was due to ongoing inflammation in vivo, cultures of normal and asthmatic bronchial epithelial cells were used to study apoptosis in vitro. In complete growth medium, these cells showed no difference in their rate of proliferation or viability. However, cells from subjects with asthma were more susceptible to the apoptotic effects of H2O2 than cells from normal control subjects (% apoptotic cells = 32.2 [8.8-54.9] versus 14.3 [6.4-24.7]; P < 0.05), even though both were similarly affected by treatment with actinomycin D. These data indicate that the susceptibility of asthmatic bronchial epithelium to oxidants is greater than normal. This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants.
Bucchieri
Fabio
F
School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Puddicombe
Sarah M
SM
Lordan
James L
JL
Richter
Audrey
A
Buchanan
Diane
D
Wilson
Susan J
SJ
Ward
Jon
J
Zummo
Giovanni
G
Howarth
Peter H
PH
Djukanović
Ratko
R
Holgate
Stephen T
ST
Davies
Donna E
DE
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001249:Asthma / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology / Q000503:physiopathology*; D003585:Cell Biology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases