Tsurutani Mayu, Horie Haruka, Ogawa Kazushige
Laboratory of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
Laboratory of Veterinary Anatomy, College of Life, Environment and Advanced Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
Biomedicines. 2021 Sep 16;9(9):1241. doi: 10.3390/biomedicines9091241.
Tissue-resident macrophages (Mø) originating from foetal precursors are maintained by self-renewal under tissue/organ-specific microenvironments (niches). We recently developed a simple propagation method applicable to tissue-resident Mø by co-culturing. Here, we examined the properties of lung tissue-resident Mø propagated by co-culturing with lung interstitial cells. The intracardially and intratracheally perfused lung from BALB/c and C57BL/6 mice could minimise the contamination of alveolar Mø and lung monocytes. Lung tissue-resident Mø could be largely propagated under standard culture media along with the propagation of lung interstitial cells demonstrating a fibroblastic morphology. Propagated lung Mø showed characteristic expression properties for Mø/monocyte markers: high expressions of CD11b, CD64 and CD206; substantial expressions of Mertk; and negative expressions of Ly6C, MHC II and Siglec-F. These properties fit with those of lung interstitial Mø of a certain population that can undergo self-renewal. Propagated fibroblastic cells by co-culturing with lung Mø possessed niche properties such as and expression. Propagated lung Mø from both the mouse types were polarised to an M2 phenotype highly expressing arginase 1 without M2 inducer treatment, whereas the M1 inducers significantly increased the iNOS-positive cell percentages in C57BL/6 mice relative to those in BALB/c mice. This is the first study to demonstrate fundamental properties of lung tissue-resident Mø propagated by co-culturing. Propagated lung Mø showing features of lung interstitial Mø can serve as an indispensable tool for investigating SARS-CoV-2 diseases, although lung interstitial Mø have gained little attention in terms of their involvement in SARS-CoV-2 disease pathology, in contrast to alveolar and recruited Mø.
源自胎儿前体的组织驻留巨噬细胞（Mø）在组织/器官特异性微环境（生态位）下通过自我更新得以维持。我们最近开发了一种通过共培养适用于组织驻留Mø的简单增殖方法。在此，我们研究了与肺间质细胞共培养增殖的肺组织驻留Mø的特性。来自BALB/c和C57BL/6小鼠的心内和气管内灌注肺可将肺泡Mø和肺单核细胞的污染降至最低。肺组织驻留Mø在标准培养基中可大量增殖，同时伴有呈成纤维细胞形态的肺间质细胞的增殖。增殖的肺Mø显示出Mø/单核细胞标志物的特征性表达特性：CD11b、CD64和CD206高表达；Mertk大量表达；Ly6C、MHC II和Siglec-F阴性表达。这些特性与特定群体中可进行自我更新的肺间质Mø的特性相符。与肺Mø共培养增殖的成纤维细胞具有诸如 和 表达等生态位特性。两种小鼠类型增殖的肺Mø在未用M2诱导剂处理的情况下均极化为高表达精氨酸酶1的M2表型，而M1诱导剂相对于BALB/c小鼠显著增加了C57BL/6小鼠中诱导型一氧化氮合酶（iNOS）阳性细胞百分比。这是第一项证明通过共培养增殖的肺组织驻留Mø基本特性的研究。尽管与肺泡Mø和募集的Mø相比，肺间质Mø在参与SARS-CoV-2疾病病理学方面很少受到关注，但显示肺间质Mø特征的增殖肺Mø可作为研究SARS-CoV-2疾病不可或缺的工具。
