Department of Pediatrics/Newborn Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Dev Neurosci. 2013;35(2-3):265-71. doi: 10.1159/000350928. Epub 2013 May 25.
Mast cells are immune cells of hematopoietic origin that circulate as precursor cells prior to migration into vascularized tissues where they mature and undergo terminal differentiation in response to different cytokines within the local environment. Mast cells are well known as important regulators of inflammatory processes in peripheral tissues and recent studies support the involvement of mast cells in mediating the inflammatory response to cerebral hypoxia-ischemia in both the neonatal and adult brain. To better study mast cell function in vivo, it is important to be able to identify their environment-specific phenotype, as well as to study their interaction with other neural cells in vitro. Previous such studies of mast cells have relied on mast cells isolated from gut or bone marrow, or on a number of mast cell lines, all of which may behave differently from brain mast cells. The purpose of this study was to develop a technique for the isolation of mast cells from neonatal rat brain and to characterize these cells following hypoxia and hypoxia-ischemia. We adapted a previously described technique of coupling an antibody to the mast cell-specific FcεR1 receptor to a MACS microbead for the selective removal of intact mast cells from a neonatal brain preparation. We have isolated toluidine blue-positive brain mast cells that provide substrate for both protein analysis and in vitro studies. These cells express proteins previously used to specifically identify microglia in the brain, Iba-1 and coronin-1a. A subpopulation of mast cells in vivo also expresses Iba-1. Thus, we report a novel method for isolation of brain mast cells suitable for the study of mast cell phenotype under a variety of conditions. Further, we suggest that the use of proteins such as Iba-1 for the identification of microglia in the brain includes the caveat that mast cells may also be detected.
肥大细胞是造血来源的免疫细胞,在迁移到血管化组织中成熟并在局部环境中的不同细胞因子作用下进行终末分化之前,作为前体细胞循环。肥大细胞是外周组织炎症过程的重要调节剂,最近的研究支持肥大细胞参与调节新生儿和成年大脑缺氧缺血后的炎症反应。为了更好地研究肥大细胞的体内功能,重要的是能够识别其环境特异性表型,并研究其与体外其他神经细胞的相互作用。以前对肥大细胞的此类研究依赖于从肠道或骨髓中分离的肥大细胞,或依赖于许多肥大细胞系,所有这些细胞可能与大脑肥大细胞的行为不同。本研究旨在开发一种从新生大鼠大脑中分离肥大细胞的技术,并研究这些细胞在缺氧和缺氧缺血后的表型。我们改进了先前描述的技术,即将针对肥大细胞特异性 FcεR1 受体的抗体与 MACS 微珠偶联,以从新生脑制剂中选择性去除完整的肥大细胞。我们已经分离出甲苯胺蓝阳性的脑肥大细胞,为蛋白质分析和体外研究提供了基质。这些细胞表达以前用于特异性识别大脑中小胶质细胞的蛋白质,即 Iba-1 和 coronin-1a。体内的肥大细胞亚群也表达 Iba-1。因此,我们报告了一种从大脑中分离肥大细胞的新方法,适用于在各种条件下研究肥大细胞表型。此外,我们认为使用 Iba-1 等蛋白质来鉴定大脑中的小胶质细胞存在一个警告,即肥大细胞也可能被检测到。