Acrolein in cigarette smoke attenuates the innate immune responses mediated by surfactant protein D
Acrolein in cigarette smoke attenuates the innate immune responses mediated by surfactant protein D
复制标题
香烟烟雾中的丙烯醛会减弱表面活性蛋白 D 介导的先天免疫反应
DOI：
10.1016/j.bbagen.2020.129699
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nakano Miyako
中科院分区：
文献类型：
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作者：
Takamiya Rina;Takahashi Motoko;Maeno Toshitaka;Saito Atsushi;Kato Masaki;Shibata Takahiro;Uchida Koji;Ariki Shigeru;Nakano Miyako
表面活性物质蛋白(SP)A和D属于集合素家族蛋白，在肺内天然免疫反应中发挥重要作用。我们先前已经证明，香烟烟雾(CS)增加了SP-A的丙烯醛修饰，从而损害了该蛋白的天然免疫能力。在本研究中，我们重点研究了CS及其组分丙烯醛对另一种集合素SP-D先天免疫功能的影响。方法用醛反应探针检测CS染毒1周小鼠肺组织中醛修饰的SP-D，以确定醛是否直接影响SP-D。用Western印迹、高效液相色谱-电喷雾电离串联质谱法和蓝色天然聚丙烯酰胺凝胶电泳法测定CS提取物(CSE)和丙烯醛暴露的重组人(H)SP-D的结构变化。结果染毒1周的小鼠肺组织中可检测到丙醛修饰的SP-D和SP-A。将HSP-D暴露于CSE或丙烯醛后，HSP-D的高分子量增加，丙烯醛引起HSP-D中5个赖氨酸残基的修饰。这些修饰破坏了SP-D的多聚体结构，减弱了其抑制细菌生长和激活巨噬细胞吞噬功能的能力。结论CS诱导SP-D的丙烯醛修饰，进而导致SP-D的结构和功能缺陷。这些结果表明，CS诱导的SP-D的结构和功能缺陷与CS暴露后肺的天然免疫反应功能障碍有关。
BackgroundSurfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D.MethodsTo determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis.ResultsAldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis.ConclusionCS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D.General SignificanceThese results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.