Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions.
Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions.
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DOI：
10.1038/s41419-021-03528-8
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发表时间：
2021-03-19
影响因子：
9
通讯作者：
Vermeren S
中科院分区：
文献类型：
--
作者：
Karmakar U;Chu JY;Sundaram K;Astier AL;Garside H;Hansen CG;Dransfield I;Vermeren S
持续的嗜酸性炎症驱动以丰富的免疫复合物为特征的自身免疫性疾病中的宿主损伤。不溶性免疫复合物（iIC）有效激活促炎性中性粒细胞效应子功能。我们和其他人已经表明，iIC还通过刺激中性粒细胞凋亡促进炎症消退。我们在此证明，iIC触发Fcγ RIIa依赖性中性粒细胞巨胞饮作用，导致iIC快速摄取和随后降解。我们提供的证据表明，同时iIC诱导的中性粒细胞凋亡是不同的吞噬诱导的细胞死亡。首先，iIC的摄取通过Fcγ RII刺激的巨胞饮作用而非吞噬作用发生。第二，活性氧的产生，而不是iIC-内化是iIC诱导的中性粒细胞凋亡的先决条件。我们的研究结果确定了一种以前未知的机制，通过这种机制，中性粒细胞可以从循环中清除促炎性iIC。iIC清除和iIC诱导的中性粒细胞凋亡可能共同作用，以防止响应iIC的嗜中性粒细胞炎症的潜在升级。
Persistent neutrophilic inflammation drives host damage in autoimmune diseases that are characterized by abundant immune complexes. Insoluble immune complexes (iICs) potently activate pro-inflammatory neutrophil effector functions. We and others have shown that iICs also promote resolution of inflammation via stimulation of neutrophil apoptosis. We demonstrate here that iICs trigger FcγRIIa-dependent neutrophil macropinocytosis, leading to the rapid uptake, and subsequent degradation of iICs. We provide evidence that concurrent iIC-induced neutrophil apoptosis is distinct from phagocytosis-induced cell death. First, uptake of iICs occurs by FcγRII-stimulated macropinocytosis, rather than phagocytosis. Second, production of reactive oxygen species, but not iIC-internalization is a pre-requisite for iIC-induced neutrophil apoptosis. Our findings identify a previously unknown mechanism by which neutrophils can remove pro-inflammatory iICs from the circulation. Together iIC clearance and iIC-induced neutrophil apoptosis may act to prevent the potential escalation of neutrophilic inflammation in response to iICs.
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影响因子：
7.8
作者：
Graham, I L;Lefkowith, J B;Anderson, D C;Brown, E J
通讯作者：
Brown, E J
影响因子：
8.8
作者：
Chu JY;Dransfield I;Rossi AG;Vermeren S
通讯作者：
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影响因子：
4
作者：
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Kay, Robert R.
影响因子：
20.3
作者：
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通讯作者：
Olsson, Inge
DOI：
10.1186/1476-9255-7-32
发表时间：
2010-07-07
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Tsang JL;Parodo JC;Marshall JC
通讯作者：
Marshall JC