Postlethwait E M, Langford S D, Jacobson L M, Bidani A
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX.
Free Radic Biol Med. 1995 Nov;19(5):553-63. doi: 10.1016/0891-5849(95)00058-6.
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.
吸入的二氧化氮通过一种依赖自由基的反应机制被吸收，该机制将初始氧化事件定位在肺表面衬里层（SLL）的细胞外空间。由于二氧化氮本身在吸收后会被消除，很可能SLL衍生的反应产物对二氧化氮诱导的肺损伤的发生至关重要。我们利用分析气相中二氧化氮消失的速率来确定大鼠SLL内的优先吸收底物。通过支气管肺泡灌洗获得SLL，并将其用作无细胞复合物或在成分处理后使用[（i）透析，用（ii）N-乙基马来酰亚胺、（iii）抗坏血酸氧化酶、（iv）尿酸酶或（v）组合ii + iii处理]。在纯化学系统中研究了特定的SLL成分。暴露是在二氧化氮为限制试剂并以一级动力学消失的条件下进行的（[NO2]0≤10 ppm）。还原型谷胱甘肽和抗坏血酸是大鼠SLL的主要吸收底物。非巯基氨基酸和二棕榈酰磷脂酰胆碱的吸收活性可忽略不计。虽然尿酸以及维生素A和E表现出快速的吸收动力学，但它们在SLL中的低浓度排除了可观的直接相互作用。不饱和脂肪酸可能占吸收的≤20%。结果表明，水溶性低分子量抗氧化剂是驱动二氧化氮吸收的优先底物。因此，它们因接触二氧化氮而产生自由基，可能参与引发二氧化氮诱导的级联反应，从而导致上皮损伤。
