Pharmacology and Experimental Therapeutics Unit, School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Pharmacol Res. 2023 Mar;189:106691. doi: 10.1016/j.phrs.2023.106691. Epub 2023 Feb 10.
Mast cells are initiators and main effectors of allergic inflammation, together with eosinophils, with whom they can interact in a physical and soluble cross-talk with marked pro-inflammatory features, the Allergic Effector Unit. The pro-resolution role of mast cells, alone or in co-culture with eosinophils, has not been characterized yet.
We aimed to investigate select pro-resolution pathways in mast cells in vitro and in vivo in allergic inflammation.
In vitro, we employed human and murine mast cells and analyzed release of resolvin D1 and expression of 15-lipoxygenase after IgE-mediated activation. We performed co-culture of IgE-activated mast cells with peripheral blood eosinophils and investigated 15-lipoxygenase expression and Resolvin D1 release. In vivo, we performed Ovalbumin/Alum and Ovalbumin/S. aureus enterotoxin B allergic peritonitis model in Wild Type mice following a MC "overshoot" protocol.
We found that IgE-activated mast cells release significant amounts of resolvin D1 30 min after activation, while 15-lipoxygenase expression remained unchanged. Resolvin D1 release was found to be decreased in IgE-activated mast cells co-cultured with peripheral blood eosinophils for 30 min In vivo, mast cell-overshoot mice exhibited a trend of reduced inflammation, together with increased peritoneal resolvin D1 release.
Mast cells can actively contribute to resolution of allergic inflammation by releasing resolvin D1.
肥大细胞是过敏炎症的启动者和主要效应细胞,与嗜酸性粒细胞一起,它们可以通过具有显著促炎特征的物理和可溶性串扰相互作用,即过敏效应单元。肥大细胞的促解决作用,无论是单独作用还是与嗜酸性粒细胞共培养,尚未得到明确。
我们旨在研究体外和过敏炎症中的肥大细胞中的特定促解决途径。
在体外,我们使用人源和鼠源肥大细胞,并分析 IgE 介导的激活后 15-脂氧合酶的释放和表达。我们进行 IgE 激活的肥大细胞与外周血嗜酸性粒细胞的共培养,并研究 15-脂氧合酶表达和 Resolvin D1 释放。在体内,我们在肥大细胞“过表达”方案后,在野生型小鼠中进行卵清蛋白/明矾和卵清蛋白/金黄色葡萄球菌肠毒素 B 过敏性腹膜炎模型。
我们发现 IgE 激活的肥大细胞在激活后 30 分钟释放大量的 Resolvin D1,而 15-脂氧合酶表达保持不变。在 IgE 激活的肥大细胞与外周血嗜酸性粒细胞共培养 30 分钟后,发现 Resolvin D1 释放减少。在体内,肥大细胞过表达小鼠表现出炎症减轻的趋势,同时腹膜腔中 Resolvin D1 释放增加。
肥大细胞通过释放 Resolvin D1 可以积极促进过敏炎症的解决。