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首页> 美国卫生研究院文献>Cell Regulation >Roles for Ca2+ stores release and two Ca2+ influx pathways in the Fc epsilon R1-activated Ca2+ responses of RBL-2H3 mast cells.
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Roles for Ca2+ stores release and two Ca2+ influx pathways in the Fc epsilon R1-activated Ca2+ responses of RBL-2H3 mast cells.

机译：Ca2 +存储区的作用和RBL-2H3肥大细胞在FcεR1激活的Ca2 +响应中的释放和两个Ca2 +流入途径。

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Cross-linking the high affinity IgE receptor, Fc epsilon R1, with multivalent antigen induces inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-dependent release of intracellular Ca2+ stores, Ca2+ influx, and secretion of inflammatory mediators from RBL-2H3 mast cells. Here, fluorescence ratio imaging microscopy was used to characterize the antigen-induced Ca2+ responses of single fura-2-loaded RBL-2H3 cells in the presence and absence of extracellular Ca2+ (Ca2+o). As antigen concentration increases toward the optimum for secretion, more cells show a Ca2+ spike or an abrupt increase in [Ca2+]i and the lag time to onset of the response decreases both in the presence and the absence of Ca2+o. When Ca2+o is absent, fewer cells respond to low antigen and the lag times to response are longer than those measured in the presence of Ca2+o, indicating that Ca2+o contributes to Ca2+ stores release. Ins(1,4,5)P3 production is not impaired by the removal of Ca2+o, suggesting that extracellular Ca2+ influences Ca2+ stores release via an effect on the Ins(1,4,5)P3 receptor. Stimulation with low concentrations of antigen can lead, only in the presence of Ca2+o, to a small, gradual increase in [Ca2+]i before the abrupt spike response that indicates store release. We propose that this small, initial [Ca2+]i increase is due to receptor-activated Ca2+ influx that precedes and may facilitate Ca2+ stores release. A mechanism for capacitative Ca2+ entry also exists in RBL-2H3 cells. Our data suggest that a previously undescribed response to Fc epsilon R1 cross-linking, inhibition of Ca2+ stores refilling, may be involved in activating capacitative Ca2+ entry in antigen-stimulated RBL-2H3 cells, thus providing the elevated [Ca2+]i required for optimal secretion. The existence of both capacitative entry and Ca2+ influx that can precede Ca2+ release from intracellular stores suggests that at least two mechanisms of stimulated Ca2+ influx are present in RBL-2H3 cells.
机译：高亲和力IgE受体Fc epsilon R1与多价抗原的交联诱导肌醇1,4,5-三磷酸[Ins（1,4,5）P3]依赖性释放细胞内Ca2 +储存，Ca2 +流入和分泌RBL-2H3肥大细胞的炎症介质。在这里，荧光比率成像显微镜用于表征存在和不存在细胞外Ca2 +（Ca2 + o）的单个呋喃2加载的RBL-2H3细胞的抗原诱导的Ca2 +反应。随着抗原浓度朝着分泌的最佳方向增加，更多的细胞显示Ca2 +尖峰或[Ca2 +] i突然增加，并且在存在和不存在Ca2 + o的情况下，响应开始的滞后时间都会减少。当不存在Ca2 + o时，对低抗原的细胞响应较少，并且响应的滞后时间比在有Ca2 + o的情况下测得的响应时间更长，这表明Ca2 + o有助于Ca2 +存储的释放。去除Ca2 + o不会损害Ins（1,4,5）P3的产生，这表明细胞外Ca2 +通过对Ins（1,4,5）P3受体的影响来影响Ca2 +存储的释放。仅在Ca2 + o存在的情况下，用低浓度的抗原刺激才能导致[Ca2 +] i的小幅逐渐增加，然后才表明存储释放。我们建议，这种小的，最初的[Ca2 +] i增加是由于先于受体激活的Ca2 +大量涌入，并可能促进Ca2 +存储的释放。 RBL-2H3细胞中也存在一种能进入Ca2 +的机制。我们的数据表明，先前未描述的对FcεR1交联的反应（抑制Ca2 +储库的重新填充）可能与激活抗原刺激的RBL-2H3细胞中的电容性Ca2 +进入有关，从而提供了最佳所需的升高的[Ca2 +] i。分泌。能够进入Ca2 +从细胞内储存释放的电容性进入和Ca2 +内流均存在，这表明RBL-2H3细胞中至少存在两种​​刺激Ca2 +内流的机制。

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