半胱氨酰白三烯通过颗粒膜表达的受体发挥作用，从无细胞的人嗜酸性粒细胞颗粒中引发分泌。
Cysteinyl leukotrienes acting via granule membrane-expressed receptors elicit secretion from within cell-free human eosinophil granules.
机构信息
Division of Allergy and Inflammation, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
出版信息
J Allergy Clin Immunol. 2010 Feb;125(2):477-82. doi: 10.1016/j.jaci.2009.11.029.
BACKGROUND
Cysteinyl leukotrienes (cysLTs) are recognized to act via receptors (cysLTRs) expressed on cell surface plasma membranes. Agents that block cysLT(1) receptor (cysLT(1)R) are therapeutics for allergic disorders. Eosinophils contain multiple preformed proteins stored within their intracellular granules. Cell-free eosinophil granules are present extracellularly as intact membrane-bound organelles in sites associated with eosinophil infiltration, including asthma, rhinitis, and urticaria, but have unknown functional capabilities.
OBJECTIVE
We evaluated the expression of cysLTRs on eosinophil granule membranes and their functional roles in eliciting protein secretion from within eosinophil granules.
METHODS
We studied secretory responses of human eosinophil granules isolated by subcellular fractionation. Granules were stimulated with cysLTs, and eosinophil cationic protein and cytokines were measured in the supernatants. Receptor expression on granule membranes and eosinophils was evaluated by flow cytometry and Western blot.
RESULTS
We report that receptors for cysLTs, cysLT(1)R, cysLT(2) receptor, and the purinergic P2Y12 receptor, are expressed on eosinophil granule membranes. Leukotriene (LT) C(4) and extracellularly generated LTD(4) and LTE(4) stimulated isolated eosinophil granules to secrete eosinophil cationic protein. MRS 2395, a P2Y12 receptor antagonist, inhibited cysLT-induced eosinophil cationic protein release. Montelukast, likely not solely as an inhibitor of cysLT(1)R, inhibited eosinophil cationic protein release elicited by LTC(4) and LTD(4) as well as by LTE(4).
CONCLUSION
These studies identify previously unrecognized sites of localization, the membranes of intracellular eosinophil granule organelles, and function for cysLT-responsive receptors that mediate cysteinyl leukotriene-stimulated secretion from within eosinophil granules, including those present extracellularly.
背景
半胱氨酰白三烯（cysLTs）被认为通过细胞表面质膜上表达的受体（cysLTRs）发挥作用。阻断半胱氨酰白三烯（1）受体（cysLT（1）R）的药物是治疗过敏疾病的药物。嗜酸性粒细胞含有储存在细胞内颗粒中的多种预先形成的蛋白质。细胞外的无细胞嗜酸性粒细胞颗粒作为完整的膜结合细胞器存在于与嗜酸性粒细胞浸润相关的部位，包括哮喘、鼻炎和荨麻疹，但它们的功能能力未知。
目的
我们评估了嗜酸性粒细胞颗粒膜上 cysLTR 的表达及其在引发嗜酸性粒细胞颗粒内蛋白分泌中的功能作用。
方法
我们通过亚细胞分级分离研究了人嗜酸性粒细胞颗粒的分泌反应。用 cysLTs 刺激颗粒，测量上清液中的嗜酸性粒细胞阳离子蛋白和细胞因子。通过流式细胞术和 Western blot 评估颗粒膜和嗜酸性粒细胞上的受体表达。
结果
我们报告说，cysLTs 的受体，cysLT（1）R、cysLT（2）受体和嘌呤能 P2Y12 受体，都表达在嗜酸性粒细胞颗粒膜上。白三烯（LT）C（4）和细胞外生成的 LTD（4）和 LTE（4）刺激分离的嗜酸性粒细胞颗粒分泌嗜酸性粒细胞阳离子蛋白。P2Y12 受体拮抗剂 MRS 2395 抑制 cysLT 诱导的嗜酸性粒细胞阳离子蛋白释放。孟鲁司特可能不仅作为 cysLT（1）R 的抑制剂，还抑制 LTC（4）和 LTD（4）以及 LTE（4）引起的嗜酸性粒细胞阳离子蛋白释放。
结论
这些研究确定了以前未被识别的定位部位，即细胞内嗜酸性粒细胞颗粒细胞器的膜，以及介导半胱氨酰白三烯刺激嗜酸性粒细胞颗粒内分泌的 cysLT 反应性受体的功能，包括存在于细胞外的受体。
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