Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages.
Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages.
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DOI：
10.1371/journal.pone.0147358
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yamakawa M
中科院分区：
文献类型：
--
作者：
Aung NY;Ohe R;Meng H;Kabasawa T;Yang S;Kato T;Yamakawa M
在免疫系统中，包括NRP-1和NRP-2在内的NRP在胸腺细胞、树突状细胞、调节性T细胞和巨噬细胞中均有表达。它们对肿瘤细胞周围免疫细胞的作用因其配体的不同而不同，包括促血管生成、肿瘤进展和抗血管生成。尽管已经研究了NRPs在恶性肿瘤和免疫系统上的表达，但基于PubMed的文献查询没有找到任何描述NRPs在组织特异性巨噬细胞上表达的文章。本研究的目的是(1)检测NRPs在脑、肝、脾、淋巴结和肺的组织特异性巨噬细胞上的表达；(2)观察NRPs在肺泡巨噬细胞(AM)、支气管巨噬细胞(BMS)、间质巨噬细胞(IMS)、血管内巨噬细胞(IVMS)和巨噬细胞亚群(M1、M2和Mox)中的表达；(Iii)检测NRPs与树突状细胞特异性ICAM-3-抓取非整合素(DC-SIGN)在AM中的共表达。用免疫组织化学方法(IHC)在组织特异性巨噬细胞中的AM中特异性地检测到这两种NRP。逆转录-聚合酶链式反应(RT-PCR)和原位-聚合酶链式反应(原位-PCR)检测正常肺组织中NRPs基因的表达水平。免疫组织化学方法检测AMS、BMS和IVMS中NRP的表达。癌旁肺组织中NRPs+AM的频率明显高于炎症肺组织和正常肺组织。双重和三重免疫组化证实NRPs在肺内所有巨噬细胞亚群上均有表达。双重免疫组化显示DC-SIGN和NRPs在AM中共表达。本研究首次证实了这两种NRP在AM组织特异性巨噬细胞中的表达及其在M1、M2和Mox巨噬细胞上的表达。此外，NRPs和DC-SIGN的共同表达可能是AM起源于血单核细胞的原因。
In the immune system, neuropilins (NRPs), including NRP-1 and NRP-2, are expressed in thymocytes, dendritic cells, regulatory T cells and macrophages. Their functions on immune cells around the neoplastic cells vary into pro-angiogenesis, tumor progression and anti-angiogenesis according to their ligands. Even though NRPs expression on malignant tumors and immune system has studied, a PubMed-based literature query did not yield any articles describing NRPs expression on tissue-specific macrophages. The aims of this study were (i) to detect NRPs expression on tissue-specific macrophages in the brain, liver, spleen, lymph node and lung; (ii) to observe NRPs expression in classes of macrophages, including alveolar macrophages (AMs), bronchial macrophages (BMs), interstitial macrophages (IMs), intravascular macrophages (IVMs) and macrophage subsets (M1, M2 and Mox) in lung; and (iii) to detect the co-expression of NRPs and dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in AMs. Both NRPs were specifically detected in AMs among tissue-specific macrophages by immunohistochemistry (IHC). NRPs mRNA expression levels were characterized in normal lung by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ-polymerase chain reaction (in situ-PCR). The expression of both NRPs was detected in AMs, BMs and IVMs by IHC. The frequency of NRPs+ AMs in lung tissue adjacent to the cancer margin was significantly higher than the frequencies in inflamed and normal lung tissue. Double and triple IHC demonstrated that NRPs are expressed on all macrophage subsets in lung. Double IHC showed co-expression of DC-SIGN and NRPs in AMs. This study demonstrated for the first time the specific expression of both NRPs in AMs among tissue-specific macrophages and their expression on M1, M2 and Mox macrophages. Furthermore, the possible origin of AMs from blood monocytes could be suggested from a co-expression of NRPs and DC-SIGN.