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In vitro exposure to Hymenoptera venom and constituents activates discrete ionotropic pathways in mast cells.
Channels ( IF 3.3 ) Pub Date : 2019-06-25 , DOI: 10.1080/19336950.2019.1629225
C Jansen 1 , L M N Shimoda 1 , J Starkus 1 , I Lange 2 , N Rysavy 1 , K Maaetoft-Udsen 1 , C Tobita 1 , A J Stokes 3 , H Turner 1
Affiliation  

Calcium entry is central to the functional processes in mast cells and basophils that contribute to the induction and maintenance of inflammatory responses. Mast cells and basophils express an array of calcium channels, which mediate responses to diverse stimuli triggered by small bioactive molecules, physicochemical stimuli and immunological inputs including antigens and direct immune cell interactions. These cells are also highly responsive to certain venoms (such as Hymenoptera envenomations), which cause histamine secretion, cytokine release and an array of pro-inflammatory functional responses. There are gaps in our understanding of the coupling of venom exposure to specific signaling pathways such as activation of calcium channels. In the present study, we performed a current survey of a model mast cell line selected for its pleiotropic responsiveness to multiple pro-inflammatory inputs. As a heterogenous stimulus, Hymenoptera venom activates multiple classes of conductance at the population level but tend to lead to the measurement of only one type of conductance per cell, despite the cell co-expressing multiple channel types. The data show that ICRAC, IARC, and TRPV-like currents are present in the model mast cell populations and respond to venom exposure. We further assessed individual venom components, specifically secretagogues and arachidonic acid, and identified the conductances associated with these stimuli in mast cells. Single-cell calcium assays and immunofluorescence analysis show that there is heterogeneity of channel expression across the cell population, but this heterogeneity does not explain the apparent selectivity for specific channels in response to exposure to venom as a composite stimulus.



中文翻译:

膜翅目毒液和成分的体外暴露会激活肥大细胞中离散的离子型通路。

钙进入对于肥大细胞和嗜碱性粒细胞的功能过程至关重要,这些过程有助于诱导和维持炎症反应。肥大细胞和嗜碱性粒细胞表达一系列钙通道,它们介导对由小生物活性分子、物理化学刺激和免疫输入(包括抗原和直接免疫细胞相互作用)触发的各种刺激的反应。这些细胞对某些毒液(如膜翅目毒液),导致组胺分泌、细胞因子释放和一系列促炎功能反应。我们对毒液暴露与特定信号通路(如钙通道激活)的耦合的理解存在差距。在本研究中,我们对模型肥大细胞系进行了一项当前调查,该细胞系因其对多种促炎输入的多效反应而选择。作为异源刺激,膜翅目毒液在种群水平激活多种类型的电导,但往往导致每个细胞仅测量一种类型的电导,尽管细胞共表达多种通道类型。数据显示 I CRAC , I ARC,和 TRPV 样电流存在于模型肥大细胞群中,并对毒液暴露作出反应。我们进一步评估了单个毒液成分,特别是促分泌素和花生四烯酸,并确定了与肥大细胞中这些刺激相关的电导。单细胞钙测定和免疫荧光分析表明,细胞群中通道表达的异质性,但这种异质性并不能解释特定通道在暴露于毒液作为复合刺激时具有明显的选择性。

更新日期:2019-06-25
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