IN-VIVO ANTIOXIDANT GENE-EXPRESSION IN HUMAN AIRWAY EPITHELIUM OF NORMAL INDIVIDUALS EXPOSED TO 100-PERCENT O-2

Human bronchial epithelium is exquisitely sensitive to high O2 levels, with tracheobronchitis usually developing after 12 h of exposure to 1 00% O2. To evaluate whether this vulnerability results from inability of the bronchial epithelium to provide adequate antioxidant protection , we quantified antioxidant gene expression in bronchial epithelium of normal volunteers at baseline and after exposure to 100% O2 in vivo. After 14.8 +/- 0.2 h of 100% O2, 24 of 33 individuals had evidence of tracheobronchitis. Baseline gene expression of CuZn superoxide dismuta se (SOD), MnSOD, and catalase in bronchial epithelium was very low (Cu ZnSOD 4.1 +/-0.8 transcripts/cell, MnSOD 5.1 +/- 0.9, catalase 1.3 +/- 0.2), with control gamma-actin expression relatively abundant (50 +/- 6 transcripts/cell). Importantly, despite 100% O2 exposure sufficient to cause tracheobronchitis in most individuals, antioxidant mRNA tran scripts/cell in bronchial epithelium did not increase (P > 0.5). Catal ase activity in bronchial epithelium did not change after exposure to hyperoxia (P > 0.05). Total SOD activity increased mildly (P < 0.01) b ut not sufficiently to protect the epithelium. Together, the very low levels of expression of intracellular antioxidant enzymes and the inab ility to upregulate expression at the mRNA level with oxidant stress l ikely have a role in human airway epithelium susceptibility to hyperox ia.