Bankova L G, Dwyer D F, Liu A Y, Austen K F, Gurish M F
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA.
Mucosal Immunol. 2015 May;8(3):596-606. doi: 10.1038/mi.2014.91. Epub 2014 Oct 8.
In contrast to resident constitutive mast cells (CMCs), mucosal MCs (MMCs) appear in the lung and trachea of sensitized mice only following inhalation challenge. We monitored the influx and maturation of MCs by their expression of Kit, FcɛRI, β7-integrin and side scatter (SSC) by flow cytometry. Influx of MC progenitors (MCps) (FcɛRI(lo), Kit(int), β7(hi), and SSC(lo)) peaks 1 day after challenges and subsides to baseline by day 7 after challenge. The mature MMCs appear as a distinct population on day 7 and peak at day 14 with higher SSC and FcɛRI expression, but lower β7 and Kit expression. A distinct transitional population is present between 1 and 7 days after challenge. Maturation occurs more rapidly in the trachea. The resident tracheal CMCs had higher SSC, FcɛRI, and Kit and lower β7-integrin expression than the MMCs. By histology, the MMCs follow similar kinetics to the flow cytometry-identified mature MMCs and are notably persistent for >42 days. Steroid treatment reduced inflammation and MCp influx but had no effect on established MMCs. Thus, changes in SSC, FcɛRI, and Kit together with the expression of αE/α4:β7-integrins characterizes the development of induced MMCs from MCps and distinguishes them from resident CMCs in the trachea and large airways.
与驻留性组成型肥大细胞(CMC)不同,黏膜肥大细胞(MMC)仅在致敏小鼠经吸入激发后才出现在肺和气管中。我们通过流式细胞术检测肥大细胞表达Kit、FcɛRI、β7整合素和侧向散射光(SSC)来监测其流入和成熟情况。肥大细胞祖细胞(MCp)(FcɛRI(低)、Kit(中)、β7(高)和SSC(低))在激发后1天流入达到峰值,并在激发后第7天降至基线水平。成熟的MMC在第7天作为一个独特的群体出现,并在第14天达到峰值,其SSC和FcɛRI表达较高,但β7和Kit表达较低。在激发后1至7天存在一个独特的过渡群体。气管中的成熟速度更快。与MMC相比,驻留的气管CMC具有更高的SSC、FcɛRI和Kit,以及更低的β7整合素表达。通过组织学观察,MMC的动力学与流式细胞术鉴定的成熟MMC相似,并且在>42天内显著持续存在。类固醇治疗可减轻炎症和MCp流入,但对已形成的MMC没有影响。因此,SSC、FcɛRI和Kit的变化以及αE/α4:β7整合素的表达共同表征了由MCp诱导产生的MMC的发育过程,并将它们与气管和大气道中的驻留CMC区分开来。