Mer-mediated eosinophil efferocytosis regulates resolution of allergic airway inflammation.
Mer-mediated eosinophil efferocytosis regulates resolution of allergic airway inflammation.
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DOI：
10.1016/j.jaci.2018.01.029
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Rossi AG
中科院分区：
文献类型：
--
作者：
Felton JM;Lucas CD;Dorward DA;Duffin R;Kipari T;Vermeren S;Robb CT;MacLeod KG;Serrels B;Schwarze J;Haslett C;Dransfield I;Rossi AG
嗜酸性粒细胞在过敏性疾病（包括哮喘）的传播中起着重要作用。嗜酸性粒细胞的募集和保留都调节肺嗜酸性粒细胞增多，但吞噬细胞清除凋亡细胞的改变是否直接有助于过敏性气道炎症的解决，这一问题尚未探讨。在这项研究中，我们研究了受体酪氨酸激酶Mer在体内介导凋亡嗜酸性粒细胞清除和过敏性气道炎症消退中的作用，以确定凋亡细胞清除是否直接影响过敏性气道炎症的消退。肺泡和骨髓巨噬细胞用于研究MER介导的凋亡嗜酸性粒细胞的吞噬作用。通过使用卵清蛋白在小鼠中建立过敏性气道炎症消退模型。经鼻内给予标记的凋亡细胞或通过给予地塞米松驱动嗜酸性粒细胞凋亡，以确定体内凋亡细胞清除率。Mer的抑制或缺乏损害了巨噬细胞对凋亡的人和小鼠嗜酸性粒细胞的吞噬作用。Mer缺陷小鼠表现出卵白蛋白诱导的过敏性气道炎症的延迟消退，以及气道对雾化乙酰甲胆碱的反应性增加，支气管肺泡灌洗液蛋白水平增加，细胞因子产生改变，地塞米松治疗后未清除的死亡嗜酸性粒细胞过多。肺泡巨噬细胞的吞噬作用是显着的Mer依赖性，与Mer衰减凋亡细胞清除在体内，以增强炎症反应的凋亡细胞。我们证明，梅尔介导的吞噬细胞的凋亡细胞清除有助于解决过敏性气道炎症，这表明增加凋亡细胞清除是一个潜在的治疗过敏性气道炎症的治疗策略。
Eosinophils play a central role in propagation of allergic diseases, including asthma. Both recruitment and retention of eosinophils regulate pulmonary eosinophilia, but the question of whether alterations in apoptotic cell clearance by phagocytes contributes directly to resolution of allergic airway inflammation remains unexplored. In this study we investigated the role of the receptor tyrosine kinase Mer in mediating apoptotic eosinophil clearance and allergic airway inflammation resolution in vivo to establish whether apoptotic cell clearance directly affects the resolution of allergic airway inflammation. Alveolar and bone marrow macrophages were used to study Mer-mediated phagocytosis of apoptotic eosinophils. Allergic airway inflammation resolution was modeled in mice by using ovalbumin. Fluorescently labeled apoptotic cells were administered intratracheally or eosinophil apoptosis was driven by administration of dexamethasone to determine apoptotic cell clearance in vivo. Inhibition or absence of Mer impaired phagocytosis of apoptotic human and mouse eosinophils by macrophages. Mer-deficient mice showed delayed resolution of ovalbumin-induced allergic airway inflammation, together with increased airway responsiveness to aerosolized methacholine, increased bronchoalveolar lavage fluid protein levels, altered cytokine production, and an excess of uncleared dying eosinophils after dexamethasone treatment. Alveolar macrophage phagocytosis was significantly Mer dependent, with the absence of Mer attenuating apoptotic cell clearance in vivo to enhance inflammation in response to apoptotic cells. We demonstrate that Mer-mediated apoptotic cell clearance by phagocytes contributes to resolution of allergic airway inflammation, suggesting that augmenting apoptotic cell clearance is a potential therapeutic strategy for treating allergic airway inflammation.
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影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
10
作者：
Dorward DA;Lucas CD;Doherty MK;Chapman GB;Scholefield EJ;Conway Morris A;Felton JM;Kipari T;Humphries DC;Robb CT;Simpson AJ;Whitfield PD;Haslett C;Dhaliwal K;Rossi AG
通讯作者：
Rossi AG
影响因子：
4.6
作者：
Hoodless LJ;Lucas CD;Duffin R;Denvir MA;Haslett C;Tucker CS;Rossi AG
通讯作者：
Rossi AG
DOI：
10.1007/978-1-62703-845-4_10
发表时间：
2014-01-01
期刊：
NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Dorward, David A.;Rossi, Adriano G.;Lucas, Christopher D.
通讯作者：
Lucas, Christopher D.
DOI：
10.1073/pnas.1524292113
发表时间：
2016-06-07
影响因子：
11.1
作者：
Cai, Bishuang;Thorp, Edward B.;Tabas, Ira
通讯作者：
Tabas, Ira