Inhaled (NO2)-N-. is absorbed by a free radical-dependent reaction mec
hanism that localizes the initial oxidative events to the extracellula
r space of the pulmonary surface lining layer (SLL). Because (NO2)-N-.
per se is eliminated upon absorption, most likely the SLL-derived rea
ction products are critical to the genesis of (NO2)-N-.-induced lung i
njury. We utilized analysis of the rate of (NO2)-N-. disappearance fro
m the gas phase to determine the preferential absorption substrates wi
thin 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 ox
idase, (iv) uricase, or (v) combined ii + iii]. Specific SLL constitue
nts were studied in pure chemical systems. Exposures were conducted un
der conditions where (NO2)-N-. is the limiting reagent and disappears
with first-order kinetics ([NO2](0) less than or equal to 10 ppm). Red
uced glutathione and ascorbate were the principle rat SLL absorption s
ubstrates. Nonsulfhydryl amino acids and dipalmitoyl phosphatidylcholi
ne exhibited negligible absorption activity. Whereas uric acid and vit
amins A and E displayed rapid absorption kinetics, their low SLL conce
ntrations preclude appreciable direct interaction, Unsaturated fatty a
cids may account for less than or equal to 20% of absorption. The resu
lts suggest that water soluble, low molecular weight antioxidants are
the preferential substrates driving (NO2)-N-. absorption. Consequently
, their free radicals, produced as a consequence of (NO2)-N-. exposure
, may participate in initiating the (NO2)-N-.-induced cascade, which r
esults in epithelial injury.