Faculty of Medicine, Université Laval, Quebec City, Canada.
Quebec Heart and Lung Institute - Université Laval, 2725 Chemin Sainte-Foy, Quebec City, G1V 4G5, Canada.
Respir Res. 2018 Jul 3;19(1):131. doi: 10.1186/s12931-018-0833-9.
Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice.
Mice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes.
Immunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment.
Overall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure.
香烟烟雾暴露会影响肺部脂质稳态，并导致针对氧化型低密度脂蛋白（OxLDL）的肺部抗体逐渐增加。同样，在动脉粥样硬化中也观察到抗 OxLDL 抗体增加，动脉粥样硬化也是一种与吸烟和脂质稳态紊乱密切相关的疾病。几种针对氧化脂质的免疫接种策略已被证明有助于清除它们，从而减少动脉粥样硬化病变的形成。由于香烟烟雾暴露过程中会产生氧化脂质，因此我们研究了针对 OxLDL 的预防性免疫接种方案对香烟烟雾暴露引起的肺部效应的影响。
在开始急性（2 周）或亚慢性（8 周）香烟烟雾暴露方案之前，通过系统免疫接种将人 OxLDL（抗原源）和 AddaVax（佐剂）混合物或 PBS 单独用于小鼠。通过直接 ELISA 在支气管肺泡灌洗液（BAL）和血清中测量抗 OxLDL 抗体。通过测量 BAL 中的炎症细胞、肺功能以及肺结构和基质/基质相关基因的基因水平来评估香烟烟雾暴露和 OxLDL 免疫接种对肺部的影响。
OxLDL 免疫接种导致针对 OxLDL 的循环和肺部抗体明显增加，并且在香烟烟雾暴露期间持续存在。在急性或亚慢性暴露于香烟烟雾后，OxLDL 免疫接种既没有加重也没有减轻炎症反应。OxLDL 免疫接种本身对肺功能的影响与香烟烟雾暴露相似，但 OxLDL 免疫接种和香烟烟雾暴露对这些参数没有相加作用。与载体处理相比，OxLDL 免疫接种对肺组织学、气腔或基质和基质相关基因的水平没有明显影响。
总的来说，这项研究首次表明，针对 OxLDL 的预防性免疫接种方案可能会对肺功能产生有害影响，而不会对香烟烟雾暴露产生额外的影响。这项工作揭示了抗 OxLDL 抗体与香烟烟雾暴露引起的肺部反应之间复杂的动态关系。
