Seto Shintaro, Morimoto Kozo, Yoshida Tsutomu, Hiramatsu Miyako, Hijikata Minako, Nagata Toshi, Kikuchi Fumihito, Shiraishi Yuji, Kurashima Atsuyuki, Keicho Naoto
Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Front Microbiol. 2020 Jan 17;10:3081. doi: 10.3389/fmicb.2019.03081. eCollection 2019.
Tuberculosis (TB) and complex lung disease (MAC-LD) are both characterized pathologically by granuloma lesions, which are typically composed of a necrotic caseum at the center surrounded by fibrotic cells and lymphocytes. Although the histological characterization of TB and MAC-LD granulomas has been well-documented, their molecular signatures have not been fully evaluated. In this research we applied mass spectrometry-based proteomics combined with laser microdissection to investigate the unique protein markers in human mycobacterial granulomatous lesions. Comparing the protein abundance between caseous and cellular sub-compartments of mycobacterial granulomas, we found distinct differences. Proteins involved in cellular metabolism in transcription and translation were abundant in cellular regions, while in caseous regions proteins related to antimicrobial response accumulated. To investigate the determinants of their heterogeneity, we compared the protein abundance in caseous regions between TB and MAC-LD granulomas. We found that several proteins were significantly abundant in the MAC-LD caseum of which proteomic profiles were different from those of the TB caseum. Immunohistochemistry demonstrated that one of these proteins, Angiogenin, specifically localized to the caseous regions of selected MAC-LD granulomas. We also detected peptides derived from mycobacterial proteins in the granulomas of both diseases. This study provides new insights into the architecture of granulomatous lesions in TB and MAC-LD.
结核病（TB）和复杂性肺部疾病（MAC-LD）在病理学上均以肉芽肿病变为特征，这些病变通常由中央的坏死干酪样物质组成，周围环绕着纤维化细胞和淋巴细胞。尽管结核和MAC-LD肉芽肿的组织学特征已有充分记录，但其分子特征尚未得到充分评估。在本研究中，我们应用基于质谱的蛋白质组学结合激光显微切割技术来研究人类分枝杆菌肉芽肿病变中的独特蛋白质标志物。比较分枝杆菌肉芽肿干酪样和细胞亚区室之间的蛋白质丰度，我们发现了明显差异。参与转录和翻译中细胞代谢的蛋白质在细胞区域丰富，而在干酪样区域，与抗菌反应相关的蛋白质积累。为了研究其异质性的决定因素，我们比较了结核和MAC-LD肉芽肿干酪样区域的蛋白质丰度。我们发现几种蛋白质在MAC-LD干酪样中显著丰富，其蛋白质组谱与结核干酪样不同。免疫组织化学表明，这些蛋白质之一血管生成素特异性定位于选定的MAC-LD肉芽肿的干酪样区域。我们还在两种疾病的肉芽肿中检测到源自分枝杆菌蛋白质的肽段。本研究为结核和MAC-LD中肉芽肿病变的结构提供了新的见解。
