Released Myeloperoxidase Attenuates Neutrophil Migration and Accumulation in Inflamed Tissue.
Released Myeloperoxidase Attenuates Neutrophil Migration and Accumulation in Inflamed Tissue.
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DOI：
10.3389/fimmu.2021.654259
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发表时间：
2021
影响因子：
7.3
通讯作者：
Sumagin R
中科院分区：
文献类型：
--
作者：
Rehring JF;Bui TM;Galán-Enríquez CS;Urbanczyk JM;Ren X;Wiesolek HL;Sullivan DP;Sumagin R
中性粒细胞(PMN)募集到损伤部位是宿主防御的关键，然而过度的PMN活性和组织积聚会导致炎症和损伤的加剧。髓过氧化物酶(MPO)是一种PMN亲天青颗粒酶，它与过氧化氢一起形成一个强大的抗菌系统，旨在杀死摄入的细菌。有趣的是，除了由于ROS的产生而导致的细胞内对入侵微生物的杀伤和对细胞外组织的损伤之外，可溶性MPO还直接参与调节细胞反应和组织动态平衡。在目前的工作中，我们使用了几种炎症、小鼠和人PMN模型以及最先进的活体显微镜来检测MPO对PMN迁移和组织积聚的影响。我们发现，在缺乏功能性MPO(MPO基因敲除，KO小鼠)的情况下，炎性PMN组织积聚显著增强。我们确定，MPO基因敲除小鼠中性粒细胞数量的增加并不是由于生存能力的提高，而是由于迁移能力的增强。在酵母多糖诱导的腹膜炎或PMN-趋化因子CXCL1结扎肠环模型中，MPO KO小鼠的急性PMN迁移是野生型(WT)小鼠的2倍以上。利用发炎小鼠提睾肌的实时活体成像和PMN与发炎内皮细胞(ECs)的体外共培养，我们证明MPO KO小鼠的移行增加是由于增强了黏附相互作用。相反，体内和体外加入可溶性重组MPO均可减少PMN的黏附和迁移。尽管此前有人建议MPO与CD11b结合，但我们在静息和激活的PMN中CD11b的表达没有显著差异，进一步表明MPO与PMN表面的结合不是CD11b所特有的。因此，我们的数据确定MPO是PMN交易炎症的一种新的调节因子。
Neutrophil (PMN) recruitment to sites of insult is critical for host defense, however excessive PMN activity and tissue accumulation can lead to exacerbated inflammation and injury. Myeloperoxidase (MPO) is a PMN azurophilic granule enzyme, which together with H2O2, forms a powerful antimicrobial system designed to kill ingested bacteria. Intriguingly, in addition to intracellular killing of invading microorganisms and extracellular tissue damage due generation of ROS, soluble MPO has been directly implicated in modulating cellular responses and tissue homeostasis. In the current work, we used several models of inflammation, murine and human PMNs and state-of-the-art intravital microscopy to examine the effect of MPO on PMN migration and tissue accumulation. We found that in the absence of functional MPO (MPO knockout, KO mice) inflammatory PMN tissue accumulation was significantly enhanced. We determined that the elevated numbers of PMNs in MPO knockout mice was not due to enhanced viability, but due to increased migratory ability. Acute PMN migration in models of zymosan-induced peritonitis or ligated intestinal loops induced by intraluminal administration of PMN-chemokine CXCL1 was increased over 2-fold in MPO KO compared to wild type (WT) mice. Using real-time intravital imaging of inflamed mouse cremaster muscle and ex vivo PMN co-culture with inflamed endothelial cells (ECs) we demonstrate that elevated migration of MPO KO mice was due to enhanced adhesive interactions. In contrast, addition of soluble recombinant MPO both in vivo and ex vivo diminished PMN adhesion and migration. Although MPO has been previously suggested to bind CD11b, we found no significant difference in CD11b expression in either resting or activated PMNs and further showed that the MPO binding to the PMN surface is not specific to CD11b. As such, our data identify MPO as a novel regulator of PMN trafficking in inflammation.
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反应性氧化剂和髓过氧化物酶及其参与中性粒细胞外陷阱。
影响因子：
7.3
作者：
Parker H;Winterbourn CC
通讯作者：
Winterbourn CC
影响因子：
5.5
作者：
Parker, Heather;Albrett, Amelia M.;Winterbourn, Christine C.
通讯作者：
Winterbourn, Christine C.
影响因子：
56.9
作者：
Eiserich, JP;Baldus, S;Freeman, BA
通讯作者：
Freeman, BA
DOI：
10.1111/micc.12352
发表时间：
2017-04
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Meegan JE;Yang X;Coleman DC;Jannaway M;Yuan SY
通讯作者：
Yuan SY
影响因子：
3.3
作者：
Brennan, ML;Gaur, A;Reynolds, WF
通讯作者：
Reynolds, WF