NO2 reactive absorption substrates in rat pulmonary surface lining fluids.
Inhaled 'NO2 is absorbed by a free radical-dependent reaction mechanism that localizes the initial oxidative events to the extracellular space of the pulmonary surface lining layer (SLL). Because 'NO2 per se is eliminated upon absorption, most likely the SLL-derived reaction products are critical to the genesis of 'NO2-induced lung injury. We utilized analysis of the rate of 'NO2 disappearance from the gas phase to determine the preferential absorption substrates within rat SLL. SLL was obtained via bronchoalveolar lavage and was used either as the cell-free composite or after constituent manipulation [(i) dialysis, treatment with (ii) N-ethylmaleimide, (iii) ascorbate oxidase, (iv) uricase, or (v) combined ii + iii]. Specific SLL constituents were studied in pure chemical systems. Exposures were conducted under conditions where 'NO2 is the limiting reagent and disappears with first-order kinetics ([NO2]0 < or = 10 ppm). Reduced glutathione and ascorbate were the principle rat SLL absorption substrates. Nonsulfhydryl amino acids and dipalmitoyl phosphatidylcholine exhibited negligible absorption activity. Whereas uric acid and vitamins A and E displayed rapid absorption kinetics, their low SLL concentrations preclude appreciable direct interaction. Unsaturated fatty acids may account for < or = 20% of absorption. The results suggest that water soluble, low molecular weight antioxidants are the preferential substrates driving 'NO2 absorption. Consequently, their free radicals, produced as a consequence of 'NO2 exposure, may participate in initiating the 'NO2-induced cascade, which results in epithelial injury.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX.
E M
EM
Postlethwait
S D
SD
Langford
L M
LM
Jacobson
A
A
Bidani
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000280:Administration, Inhalation; D000327:Adsorption; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001204:Ascorbate Oxidase / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D005033:Ethylmaleimide / Q000494:pharmacology; D005609:Free Radicals / Q000008:administration & dosage / Q000493:pharmacokinetics; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D008433:Mathematics; D008962:Models, Theoretical; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014503:Urate Oxidase / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism
D000596:Amino Acids; D000975:Antioxidants; D005609:Free Radicals; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D014527:Uric Acid; D001204:Ascorbate Oxidase; D014503:Urate Oxidase; D005978:Glutathione; D005033:Ethylmaleimide; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide