Ozone-reactive absorption by pulmonary epithelial lining fluid constituents.
Ozone-reactive absorption by pulmonary epithelial lining fluid constituents.
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肺上皮衬里液成分对臭氧的反应性吸收。
DOI：
10.1006/taap.1995.1093
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Postlethwait,EM
中科院分区：
文献类型：
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作者：
Langford,SD;Bidani,A;Postlethwait,EM
先前的研究表明，从肺内气相吸入O3的速率主要由反应依赖性机制介导，而不是由物理溶解度、组织扩散或血流介导（Postlethwait等人，1994年，毒理学。应用药理学125，77-89）。O3与肺表面相互作用的初始位点发生在上皮衬里液（ELF）的气/液界面处。因此，我们研究了（a）ELF成分的反应性摄取是否可以解释肺摄取和（B）所选成分是否作为O3特异性吸收靶点。通过支气管肺泡灌洗获得大鼠ELF。通过将相同的灌洗液第二次{（BALF）2}和/或第三次{（BALF）3}注射到新鲜肺中，获得更浓缩形式的ELF。利用无细胞BALF和模型底物（还原型谷胱甘肽，GSH）的受控准稳态暴露（空气中的O3; 30分钟持续时间）。结果基于温度特异性分数和归一化摄取率（r）。结果表明：（1）缓冲液pH值对GSH吸收O_3有显著影响，而对BALF吸收O_3影响不大。(2)摄取显示显著的[BALF]和[GSH]依赖性。(3)分数摄取（BALF和GSH）随着[O3]的增加而减少，但绝对摄取增加。(4)吸收表现出温度依赖性。使用Arrhenius图{In（r）vs 1/T}计算活化能（Ea）和Q10。（BALF）1Ea= 3387 cal/g mol，Q10= 1.20。GSH（1 mM）Ea= 2240，Q10= 1.13。(5)增加流量以非线性方式降低摄取分数。(6)透析（1000-分子量截留）适度降低（BALF）1的摄取（−30%）。巯基消耗产生的影响最小（-10%），而抗坏血酸消耗（-37%）和巯基和抗坏血酸联合消耗（-39%）是最有效的。治疗对（BALF）3的影响较小。我们的结论是pH值，含水基质，和温度依赖性和Ea和Q10是一致的反应依赖于O3吸收ELF。ELF和完整肺之间的类似吸收特性（温度、[O3]、接触时间）表明ELF代表O3反应性吸收的主要部位。还原巯基似乎基本上不与吸入的O3相互作用。主要的吸收目标可能包括抗坏血酸、磷脂和其他中等至大分子量的成分。
Previous studies have suggested that the rate of inhaled O3absorption from the intrapulmonary gas phase is principally mediated by reaction-dependent mechanisms rather than by physical solubility, tissue diffusion, or blood flow (Postlethwait et al., 1994, Toxicol. Appl. Pharmacol. 125, 77-89). The initial site of interaction between O3and the lung surface occurs at the gas/liquid interface of the epithelial lining fluid (ELF). Therefore, we investigated (a) whether reactive uptake by ELF constituents could account for pulmonary uptake and (b) whether selected constituents acted as O3-specific absorption targets. Rat ELF was harvested by bronchoalveolar lavage. By injecting the same lavage fluid a second {(BALF)2} and/or third {(BALF)3} time into fresh lungs, a more concentrated form of ELF was obtained. Controlled quasi-steady-state exposures (O3in air; 30-min duration) of cell-free BALF and model substrates (reduced glutathione, GSH) were utilized. Results were based on temperature-specific fractional and normalized uptake rates (r). We observed the following: (1) Buffer pH substantially influenced O3absorption by GSH but by BALF only modestly. (2) Uptake displayed significant [BALF] and [GSH] dependence. (3) Fractional uptake decreased (BALF and GSH) with increasing [O3] although absolute uptake increased. (4) Absorption demonstrated temperature dependence. Arrhenius plots {In(r) vs 1/T} were used to compute activation energies (Ea) and Q10. (BALF)1Ea= 3387 cal/g mol with Q10= 1.20. GSH (1 mM) Ea= 2240 with Q10= 1.13. (5) Increasing flow reduced fractional uptake in a nonlinear fashion. (6) Dialysis (1000-molecular-weight cutoff) reduced uptake by (BALF)1moderately (−30%). Sulfhydryl depletion produced minimal effect (−10%), while ascorbate depletion (−37%) and combined sulfhydryl and ascorbate depletion (−39%) were the most effective. Treatments produced lesser effects on (BALF)3. We conclude that the pH, aqueous substrate, and temperature-dependence and the Eaand Q10are consistent with reaction-dependent O3uptake by ELF. The analogous absorption characteristic between the ELF and intact lung (temperature, [O3], contact time) suggests that the ELF represents the primary site for O3reactive absorption. Reduced sulfhydryls do not appear to substantially interact with inhaled O3. Principal absorption targets may include ascorbate, phospholipids, and other moderate to large molecular weight constituents.