IgE cross-linking critically impairs human monocyte function by blocking phagocytosis.
IgE cross-linking critically impairs human monocyte function by blocking phagocytosis.
复制标题
DOI：
10.1016/j.jaci.2012.11.037
复制
发表时间：
2013-02
影响因子：
14.2
通讯作者：
Gill, Michelle A.
中科院分区：
文献类型：
--
作者：
Pyle, David M.;Yang, Victoria S.;Gruchalla, Rebecca S.;Farrar, J. David;Gill, Michelle A.
关键词：
IgE 交联会触发许多导致过敏性疾病的细胞过程。虽然 IgE 在介导过敏反应中的作用在嗜碱性粒细胞和肥大细胞上得到了最好的描述，但高亲和力 IgE 受体在其他先天免疫细胞（包括单核细胞）上的表达表明，它可能会影响这些细胞在过敏环境中的功能。确定 IgE 交联对人单核细胞功能的影响。从健康供体血液样本中纯化的单核细胞仅使用培养基、交联抗 IgE 抗体或对照 IgG 培养 4-96 小时。测定表面CD14和CD64表达以及分泌的细胞因子浓度。通过评估以下各项来确定单核细胞功能：1) 大肠杆菌或凋亡 HEp2 细胞的吞噬作用和 2) 细胞内大肠杆菌的杀伤作用。对从血清 IgE 浓度高于正常浓度的参与者获得的单核细胞进行了选择性实验。单核细胞上的 IgE 交联增加了 CD14 表达并诱导 TNF-α、IL-6 和自动调节 IL-10 的分泌。这些影响在血清 IgE 浓度升高的个体中最为明显。相比之下，IgE 交联会降低 CD64 表达并显着损害吞噬功能，但不会破坏单核细胞杀死细菌的能力。 IgE 交联以血清 IgE 依赖性方式驱动单核细胞促炎过程和自动调节 IL-10。相反，单核细胞的吞噬功能因 IgE 交联而严重受损。我们的研究结果表明，单核细胞上的 IgE 交联可能会增强有害的炎症反应并同时削弱吞噬作用，从而导致过敏性疾病，而吞噬作用是这些细胞用来解决炎症的主要机制。
IgE cross-linking triggers many cellular processes that drive allergic disease. While the role of IgE in mediating allergic responses is best described on basophils and mast cells, expression of the high-affinity IgE receptor on other innate immune cells, including monocytes, suggests that it may impact the function of these cells in allergic environments. To determine the effect of IgE cross-linking on the function of human monocytes. Monocytes purified from healthy donor blood samples were cultured for 4–96 hr with media alone, a cross-linking anti-IgE antibody, or control IgG. Surface CD14 and CD64 expression and secreted cytokine concentrations were determined. Monocyte function was determined by assessing: 1) phagocytosis of E. coli or apoptotic HEp2 cells and 2) killing of intracellular E. coli. Select experiments were performed on monocytes obtained from participants with elevated versus normal serum IgE concentrations. IgE cross-linking on monocytes increased CD14 expression and induced secretion of TNF-á, IL-6, and autoregulatory IL-10. These effects were greatest in individuals with elevated serum IgE concentrations. In contrast, IgE cross-linking reduced CD64 expression and significantly impaired phagocytic function without disrupting the capacity of monocytes to kill bacteria. IgE cross-linking drives monocyte pro-inflammatory processes and autoregulatory IL-10 in a serum IgE-dependent manner. In contrast, monocyte phagocytic function is critically impaired by IgE cross-linking. Our findings suggest that IgE cross-linking on monocytes may contribute to allergic disease by both enhancing detrimental inflammatory responses and concomitantly crippling phagocytosis, a primary mechanism utilized by these cells to resolve inflammation.
登录
查看更多内容
影响因子：
14.2
作者：
Kulkarni, Neeta S.;Hollins, Fay;Sutcliffe, Amanda;Saunders, Ruth;Shah, Sachil;Siddiqui, Salman;Gupta, Sumit;Haldar, Pranab;Green, Ruth;Pavord, Ian;Wardlaw, Andrew;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.
影响因子：
6.1
作者：
Cheng, Y. X.;Foster, B.;Prussin, C.
通讯作者：
Prussin, C.
影响因子：
14.2
作者：
Foster, B;Metcalfe, DD;Prussin, C
通讯作者：
Prussin, C
影响因子：
14.2
作者：
Gruchalla, RS;Pongracic, J;Mitchell, H
通讯作者：
Mitchell, H
影响因子：
14.2
作者：
Fitzpatrick, Anne M.;Holguin, Fernando;Brown, Lou Ann S.
通讯作者：
Brown, Lou Ann S.