Activated Neutrophils Secrete Chitinase-Like 1 and Attenuate Liver Inflammation by Inhibiting Pro-Inflammatory Macrophage Responses.
Activated Neutrophils Secrete Chitinase-Like 1 and Attenuate Liver Inflammation by Inhibiting Pro-Inflammatory Macrophage Responses.
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DOI：
10.3389/fimmu.2022.824385
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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中性粒细胞的过度活化和募集通常被认为与多种疾病的病理学加重有关。然而，随着中性粒细胞在组织损伤修复中的作用日益受到关注，有必要进一步探讨活化的中性粒细胞在促进损伤后炎症消退中的有益作用。在这项研究中，我们发现活化的中性粒细胞在抑制肝脏炎症中具有至关重要的功能。在蛋氨酸胆碱缺乏和高脂肪（MCDHF）饮食诱导的小鼠肝脏炎症中，尾静脉注射活化的中性粒细胞（A-Neu，由1-磷酸鞘氨醇刺激）抑制肝脏中促炎细胞因子的表达，包括C-C趋化因子基序配体4，肿瘤坏死因子和一氧化氮合酶2，减轻肝损伤。然而，非活化的中性粒细胞（N-Neu）没有这些作用。在体外，促炎性巨噬细胞分别与N-Neu或A-Neu通过transwell共培养。通过使用RT-qPCR、蛋白质印迹和流式细胞仪珠阵列发现A-Neu抑制巨噬细胞的促炎表型。基因芯片分析表明，N-Neu和A-Neu之间的转录本表达水平存在系统性差异。使用GeneVenn软件显示GO术语之间的基因表达重叠，包括细胞通讯调节、细胞因子分泌、炎症反应和细胞外空间簇。我们发现S1 P激活的中性粒细胞分泌的几丁质酶样1（Chitinase-like 1，CHIL 1）可能是影响巨噬细胞促炎反应的重要介质。在MCDHF饮食诱导的小鼠肝损伤中，Chil 1 mRNA表达增加，并与中性粒细胞标志物Ly 6 g呈正相关。此外，A-Neu中CHIL 1的分泌显著增加。引人注目的是，A-Neu对巨噬细胞应答的作用通过将促炎性巨噬细胞与重组CHIL 1孵育来再现。A-Neu条件培养基与CHIL 1抗体偶联的G蛋白珠一起孵育，通过磁力分离A-Neu上清中的免疫耗竭CHIL 1，可以部分削弱A-Neu对巨噬细胞促炎细胞因子产生的抑制作用。总之，结论表明A-Neu可以通过分泌CHIL 1抑制促炎巨噬细胞反应，从而有效抑制肝脏炎症。
Excessive activation and recruitment of neutrophils are generally considered to be associated with pathological aggravation of multiple diseases. However, as the role of neutrophils in tissue injury repair is receiving increasing attention, it is necessary to further explore the beneficial role of activated neutrophils in promoting the resolution of inflammation after injury. In this study, we found that activated neutrophils have a crucial function in suppressing liver inflammation. In methionine-choline-deficient and high-fat (MCDHF) diet induced liver inflammation in mice, tail vein injection of activated neutrophils (A-Neu, stimulated by sphingosine 1-phosphate) inhibited the expressions of pro-inflammatory cytokines in the liver, including C-C chemokine motif ligand 4, tumor necrosis factor and nitric oxide synthase 2, and attenuated liver injury. However, non-activated neutrophils (N-Neu) did not have these effects. In vitro, pro-inflammatory macrophages were co-cultured with N-Neu or A-Neu by transwell, respectively. A-Neu was found to suppress the pro-inflammatory phenotype of macrophages by using RT-qPCR, western blot and cytometric bead array. Microarray analysis showed that there were systematic variations in transcript expression levels between N-Neu and A-Neu. GeneVenn software was used to show the gene expression overlap between GO terms including Regulation of Cell Communication, Cytokine Secretion, Inflammatory Response and Extracellular Space clusters. We identified that Chitinase-like 1 (CHIL1) secreted by S1P activated neutrophils may be an important mediators affecting the pro-inflammatory macrophage responses. In the injured liver of mice induced by MCDHF diet, the expression of Chil1 mRNA increased and was positively correlated with the neutrophil marker Ly6g. Moreover, the secretion of CHIL1 in A-Neu increased significantly. Strikingly, the effect of A-Neu on macrophage response was reproduced by incubating pro-inflammatory macrophages with recombinant CHIL1. A-Neu conditioned medium were incubated with CHIL1 antibody-conjugated protein G beads, magnetically separated to immunodepletion CHIL1 from the A-Neu supernatant, which can partially weaken its inhibitory effect of A-Neu on the production of macrophage pro-inflammatory cytokines. Together, the conclusions indicated that A-Neu could inhibit the pro-inflammatory macrophage responses by secreting CHIL1, thereby effectively inhibiting liver inflammation.
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DOI：
10.1084/jem.20141539
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dal-Secco D;Wang J;Zeng Z;Kolaczkowska E;Wong CH;Petri B;Ransohoff RM;Charo IF;Jenne CN;Kubes P
通讯作者：
Kubes P
DOI：
10.1002/hep.31680
发表时间：
2021-07
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
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影响因子：
25.7
作者：
Li, Changyong;Zheng, Sujun;Li, Liying
通讯作者：
Li, Liying
DOI：
10.4049/jimmunol.1201851
发表时间：
2012-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Dragomir AC;Sun R;Choi H;Laskin JD;Laskin DL
通讯作者：
Laskin DL
DOI：
10.1126/science.aar5551
发表时间：
2019-10-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cartier A;Hla T
通讯作者：
Hla T