Postlethwait E M, Cueto R, Velsor L W, Pryor W A
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0876, USA.
Am J Physiol. 1998 Jun;274(6):L1006-16. doi: 10.1152/ajplung.1998.274.6.L1006.
Recent evidence suggests that inhaled ozone (O3) does not induce toxicity via direct epithelial interactions. Reactions with epithelial lining fluid (ELF) constituents limit cellular contact and generate products, including lipid ozonation products, postulated to initiate pathophysiological cascades. To delineate specific aspects of lipid ozonation product formation and to estimate in situ surface concentrations, we studied the O3 absorption characteristics of ELF constituent mixtures and measured hexanal, heptanal, and nonanal yields as a function of ascorbic acid (AH2) concentration. Exposures of isolated rat lungs, bronchoalveolar lavage fluid (BALF) and egg phosphatidylcholine (PC) liposomes were conducted. 1) O3 absorption by AH2, uric acid, and albumin exceeded that by egg PC and glutathione. O3 reaction with egg PC occurred when AH2 concentrations were reduced. 2) Aldehydes were produced in low yield during lung and BALF exposures in a time- and O3 concentration-dependent manner. 3) Diminishing BALF AH2 content lowered O3 uptake but increased aldehyde yields. Conversely, AH2 addition to egg PC increased O3 uptake but reduced aldehyde yields. Estimations of bioactive ozonation and autoxidation product accumulation within the ELF suggested possible nanomolar to low micromolar concentrations. The use of reaction products as metrics of O3 exposure may have intrinsic sensitivity and specificity limitations. Moreover, due to the heterogenous nature of O3 reactions within the ELF, dose-response relationships may not be linear with respect to O3 absorption.
近期证据表明，吸入的臭氧（O₃）并非通过与上皮细胞的直接相互作用诱导毒性。与上皮衬液（ELF）成分的反应限制了细胞接触，并生成了一些产物，包括脂质臭氧化产物，这些产物被认为会引发病理生理级联反应。为了阐明脂质臭氧化产物形成的具体方面，并估算原位表面浓度，我们研究了ELF成分混合物的O₃吸收特性，并测量了己醛、庚醛和壬醛的产量与抗坏血酸（AH₂）浓度的函数关系。对分离的大鼠肺、支气管肺泡灌洗液（BALF）和卵磷脂（PC）脂质体进行了暴露实验。1）AH₂、尿酸和白蛋白对O₃的吸收超过了卵磷脂和谷胱甘肽。当AH₂浓度降低时，O₃与卵磷脂发生反应。2）在肺和BALF暴露过程中，醛类以时间和O₃浓度依赖性方式低产量产生。3）降低BALF中AH₂含量会降低O₃摄取，但会增加醛类产量。相反，向卵磷脂中添加AH₂会增加O₃摄取，但会降低醛类产量。对ELF中生物活性臭氧化和自氧化产物积累的估计表明，其浓度可能在纳摩尔到低微摩尔范围内。将反应产物用作O₃暴露指标可能存在内在的敏感性和特异性限制。此外，由于ELF中O₃反应的异质性，剂量反应关系可能与O₃吸收并非呈线性关系。
