Phenotypic variability in human skin mast cells
Phenotypic variability in human skin mast cells
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DOI：
10.1111/exd.12924
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Zuberbier, Torsten
中科院分区：
文献类型：
--
作者：
Babina, Magda;Guhl, Sven;Zuberbier, Torsten
肥大细胞(MC)是人体的独特成分。虽然个体间的差异可能会影响MC在其皮肤栖息地的运作方式，但到目前为止还没有对它们进行全面的调查。因此，我们开始在一大群受试者中量化皮肤MC变异性。量化和关联相关的病理生理学关键指标：c-kit、Fc epsilon RIα、Fc epsilon RI beta、Fc epsilon RI Gamma、组氨酸脱羧酶、类胰蛋白酶和乳糜酶的转录本；c-Kit、Fc epsilon RIα的表面表达；类胰蛋白酶和乳糜酶的活性；Fc epsilon RI和钙离子载体触发的组胺含量和释放。虽然受试者之间有很大的变异性，但它强烈依赖于所研究的特征(变异系数33-386%)。Fc epsilon RI的表面表达与Fc epsilon RIαmRNA含量呈正相关，组胺含量与HDC mRNA呈正相关，糜酶活性与Chymase mRNA呈正相关。此外，MC标志性基因以不同的模式共同调控。有趣的是，组胺水平与类胰蛋白酶和乳糜酶活性呈正相关，而类胰蛋白酶和乳糜酶活性似乎没有相关性。Fc epsilon RI触发的组胺释放是高度可变的，与Fc epsilon RI的表达无关，但意外地与钙离子载体引发的组胺释放密切相关。这项最全面和系统的同类工作不仅提供了对MC个体间差异的详细见解，而且还揭示了血统标志性属性之间出人意料的共同调节模式。人类之间MC的差异很可能是过敏反应和复杂皮肤病的临床反应的基础。
Mast cells (MCs) are unique constituents of the human body. While inter-individual differences may influence the ways by which MCs operate in their skin habitat, they have not been surveyed in a comprehensive manner so far. We therefore set out to quantify skin MC variability in a large cohort of subjects. Pathophysiologically relevant key features were quantified and correlated: transcripts of c-kit, Fc epsilon RI alpha, Fc epsilon RI beta, Fc epsilon RI gamma, histidine decarboxylase, tryptase, and chymase; surface expression of c-Kit, Fc epsilon RI alpha; activity of tryptase, and chymase; histamine content and release triggered by Fc epsilon RI and Ca2+ ionophore. While there was substantial variability among subjects, it strongly depended on the feature under study (coefficient of variation 33-386%). Surface expression of Fc epsilon RI was positively associated with Fc epsilon RI alpha mRNA content, histamine content with HDC mRNA, and chymase activity with chymase mRNA. Also, MC signature genes were co-regulated in distinct patterns. Intriguingly, histamine levels were positively linked to tryptase and chymase activity, whereas tryptase and chymase activity appeared to be uncorrelated. Fc epsilon RI triggered histamine release was highly variable and was unrelated to Fc epsilon RI expression but unexpectedly tightly correlated with histamine release elicited by Ca2+ ionophore. This most comprehensive and systematic work of its kind provides not only detailed insights into inter-individual variability in MCs, but also uncovers unexpected patterns of co-regulation among signature attributes of the lineage. Differences in MCs among humans may well underlie clinical responses in settings of allergic reactions and complex skin disorders alike.