Malki Agne, Fiedler Julia, Fricke Kristina, Ballweg Ines, Pfaffl Michael W, Krautwurst Dietmar
*Deutsche Forschungsanstalt für Lebensmittelchemie Leibniz Institute, Freising, Germany; and Technische Universität München, Lehrstuhl für Physiologie-Wissenschaftszentrum Weihenstephan, Freising, Germany.
*Deutsche Forschungsanstalt für Lebensmittelchemie Leibniz Institute, Freising, Germany; and Technische Universität München, Lehrstuhl für Physiologie-Wissenschaftszentrum Weihenstephan, Freising, Germany
J Leukoc Biol. 2015 Mar;97(3):533-45. doi: 10.1189/jlb.2A0714-331RR. Epub 2015 Jan 26.
Our cellular immune system has to cope constantly with foodborne substances that enter the bloodstream postprandially. Here, they may activate leukocytes via specific but yet mostly unknown receptors. Ectopic RNA expression out of gene families of chemosensory receptors, i.e., the ∼400 ORs, ∼25 TAS2R bitter-taste receptors, and the TAS1R umami- and sweet-taste receptor dimers by which we typically detect foodborne substances, has been reported in a variety of peripheral tissues unrelated to olfaction or taste. In the present study, we have now discovered, by gene-specific RT-PCR experiments, the mRNA expression of most of the Class I ORs (TAS1R) and TAS2R in 5 different types of blood leukocytes. Surprisingly, we did not detect Class II OR mRNA. By RT-qPCR, we show the mRNA expression of human chemosensory receptors and their cow orthologs in PMN, thus suggesting an evolutionary concept. By immunocytochemistry, we demonstrate that some olfactory and taste receptors are expressed, on average, in 40-60% of PMN and T or B cells and largely coexpress in the same subpopulation of PMN. The mRNA expression and the size of subpopulations expressing certain chemosensory receptors varied largely among individual blood samples, suggesting a regulated expression of olfactory and taste receptors in these cells. Moreover, we show mRNA expression of their downstream signaling molecules and demonstrate that PTX abolishes saccharin- or 2-PEA-induced PMN chemotactic migration, indicating a role for Gi-type proteins. In summary, our data suggest "chemosensory"-type subpopulations of circulating leukocytes.
我们的细胞免疫系统必须持续应对餐后进入血液的食源物质。在此,它们可能通过特定但大多未知的受体激活白细胞。化学感应受体基因家族的异位RNA表达,即我们通常用于检测食源物质的约400种嗅觉受体(OR)、约25种TAS2R苦味受体以及TAS1R鲜味和甜味受体二聚体,已在多种与嗅觉或味觉无关的外周组织中被报道。在本研究中,我们现在通过基因特异性RT-PCR实验发现,大多数I类OR(TAS1R)和TAS2R在5种不同类型的血液白细胞中存在mRNA表达。令人惊讶的是,我们未检测到II类OR mRNA。通过RT-qPCR,我们展示了人类化学感应受体及其牛直系同源物在中性粒细胞中的mRNA表达,从而提出了一个进化概念。通过免疫细胞化学,我们证明一些嗅觉和味觉受体平均在40%-60%的中性粒细胞以及T或B细胞中表达,并且在中性粒细胞的同一亚群中大量共表达。表达某些化学感应受体的亚群的mRNA表达和大小在个体血液样本中差异很大,表明这些细胞中嗅觉和味觉受体的表达受到调控。此外,我们展示了它们下游信号分子的mRNA表达,并证明百日咳毒素(PTX)消除了糖精或2-苯乙胺诱导的中性粒细胞趋化迁移,表明Gi型蛋白发挥了作用。总之,我们的数据表明循环白细胞存在“化学感应”型亚群。