Thayaparan Danya, Shen Pamela, Stämpfli Martin R, Morissette Mathieu C
Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada.
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
Respir Res. 2016 Aug 4;17(1):97. doi: 10.1186/s12931-016-0416-6.
Chronic cigarette smoke exposure is known to activate the adaptive immune system; however, the functional role of these processes is currently unknown. Given the role of oxidized lipids in driving innate inflammatory responses to cigarette smoke, we investigated whether an adaptive immune response against damaged lipids was induced following chronic cigarette smoke exposure.
Using a well-established mouse model, we showed that cigarette smoke exposure led to a progressive increase in pulmonary antibodies against oxidized low-density lipoprotein (OxLDL). Functionally, we found that intranasal delivery of an antibody against oxidized phosphatidylcholine (anti-OxPC; clone E06) increased lipid and particle uptake by pulmonary macrophages without exacerbating cigarette smoke-induced neutrophilia. We also found that anti-OxPC treatment increased particle uptake following smoking cessation. Finally, the frequency of pulmonary macrophages with internalized particles was increased after prolonged smoke exposure, at which time lung anti-OxPC responses were highest.
Altogether, this is the first report to demonstrate a non-pathogenic, and possibly protective, function of a newly identified autoantibody induced by chronic cigarette smoke exposure.
已知长期接触香烟烟雾会激活适应性免疫系统；然而，这些过程的功能作用目前尚不清楚。鉴于氧化脂质在引发对香烟烟雾的先天性炎症反应中的作用，我们研究了长期接触香烟烟雾后是否会诱导针对受损脂质的适应性免疫反应。
使用一个成熟的小鼠模型，我们发现接触香烟烟雾会导致肺部针对氧化型低密度脂蛋白（OxLDL）的抗体逐渐增加。在功能上，我们发现经鼻递送针对氧化磷脂酰胆碱的抗体（抗OxPC；克隆E06）可增加肺巨噬细胞对脂质和颗粒的摄取，而不会加剧香烟烟雾诱导的嗜中性粒细胞增多。我们还发现抗OxPC治疗在戒烟后增加了颗粒摄取。最后，长时间接触烟雾后，内化颗粒的肺巨噬细胞频率增加此时肺部抗OxPC反应最高。
总之，这是第一份证明长期接触香烟烟雾诱导的新鉴定自身抗体具有非致病性且可能具有保护功能的报告。
