Comparison of the Toponomes of Alveolar Macrophages From Wild Type and Surfactant Protein A Knockout Mice and Their Response to Infection.
Comparison of the Toponomes of Alveolar Macrophages From Wild Type and Surfactant Protein A Knockout Mice and Their Response to Infection.
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DOI：
10.3389/fimmu.2022.853611
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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肺表面活性蛋白-A(SP-A)通过调节肺泡巨噬细胞(AM)、炎症介质和其他宿主防御蛋白的表达，在肺天然免疫中发挥重要作用。顶体组成像系统(TIS)是一种连续免疫染色系统，用于研究AM顶体组，因为它表征了多个标记的定位，并将每个像素上的标记组合识别为组合分子表型(CMPS)。我们用TIS研究了野生型(WT)和SP-A基因敲除(KO)小鼠的AM顶体组以及肺炎克雷伯菌暴露后的变化。WT或KO小鼠气管内接种肺炎克雷伯菌或赋形剂，1h后经支气管肺泡灌洗获得AM。AM贴在玻片上，进行TIS分析。对图像进行分析以确定所有像素的特征。比较来自WT载体(n=3)和感染(n=3)小鼠的AM CMPS，并与来自KO(n=3)载体的AM进行比较。直方图为我们提供了一种工具来总结一组CMP中每个标记的表示。使用直方图和其他工具，我们识别了感兴趣的标记，并观察到：1)两种比较都是保守的(在所有组成员中存在)CMP，仅在车辆AM中且仅在感染AM中，或对车辆AM和感染AM都是共同的，(即，未受条件影响)。2)WT组和KO组的CMP值均随感染时间的延长而减少。3)WT组比KO AM组感染特异性更强4)比较来自WT和KO车辆的AM和感染的AM时，KO AM具有更多独有的CMP5)所有比较均显示两组患者具有相同的中医特征。KO小鼠感染AM所特有的CMPS的减少可能是KO小鼠对感染易感性的基础。然而，两个KO组都比相应的WT组拥有更多的排他性CMP，这可能表明KO正在积极努力克服某些蛋白质和CMP的缺陷，这些蛋白质和CMP因缺少SP-A而失控。此外，在对照组中共享中医的存在表明，这些中医的调节不依赖于感染或SP-A的存在或不存在。
Surfactant protein-A (SP-A) plays a critical role in lung innate immunity by regulating alveolar macrophages (AM), expression of inflammatory mediators, and other host defense proteins. The toponome imaging system (TIS), a serial immunostainer, was used to study the AM toponome because it characterizes the localization of multiple markers and identifies marker combinations in each pixel as combinatorial molecular phenotypes (CMPs). We used TIS to study the AM toponome from wild type (WT) and SP-A knockout (KO) mice and changes following Klebsiella pneumoniae exposure. WT or KO mice received intratracheal K. pneumoniae or vehicle and AM were obtained by bronchoalveolar lavage after one hour. AM were attached to slides and underwent TIS analysis. Images were analyzed to characterize all pixels. AM CMPs from WT vehicle (n=3) and infected (n=3) mice were compared to each other and to AM from KO (n=3 vehicle; n=3 infected). Histograms provided us with a tool to summarize the representation of each marker in a set of CMPs. Using the histograms and other tools we identified markers of interest and observed that: 1) Both comparisons had conserved (present in all group members) CMPs, only in vehicle AM and only in infected AM, or common to both vehicle and infected AM, (i.e., unaffected by the condition). 2) the CMP number decreased with infection in WT and KO versus vehicle controls. 3) More infection-specific CMPs in WT vs KO AM. 4) When AM from WT and KO vehicle or infected were compared, there were more unique CMPs exclusive to the KO AM. 5) All comparisons showed CMPs shared by both groups. The decrease of CMPs exclusive to infected AM in KO mice may underlie the observed susceptibility of KO mice to infection. However, both KO groups had more exclusive CMPs than the corresponding WT groups, perhaps indicating a vigorous effort by KO to overcome deficits in certain proteins and CMPs that are dysregulated by the absence of SP-A. Moreover, the presence of shared CMPs in the compared groups indicates that regulation of these CMPs is not dependent on either infection or the presence or absence of SP-A.
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