Human neutrophil FcγRIIIb regulates neutrophil extracellular trap release in response to electrospun polydioxanone biomaterials.
Human neutrophil FcγRIIIb regulates neutrophil extracellular trap release in response to electrospun polydioxanone biomaterials.
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DOI：
10.1016/j.actbio.2021.06.007
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发表时间：
2021-08
影响因子：
9.7
通讯作者：
Bowlin GL
中科院分区：
文献类型：
--
作者：
Fetz AE;Radic MZ;Bowlin GL
在急性炎症反应期间，中性粒细胞胞外陷阱（NET）的释放是生物材料表面的促炎、预处理事件。因此，通过生物材料设计调节 NET 释放是增强生物材料引导的原位组织再生的一种策略。在这项研究中，探索了不同纤维尺寸的电纺聚二氧环己酮生物材料上的 IgG 吸附作为体外人中性粒细胞 NET 释放的调节剂。通过调节吸附的 IgG，释放 NET 的倾向会增加或减少，这表明 IgG 和 NET 形成之间存在功能联系。阻断 FcγRIIIb 可减少纤维大小依赖性 NET 释放，但阻断 FcγRI、FcγRIIa 或 Mac-1 (CD11b/CD18) 则不会减少，表明特定受体介导中性粒细胞反应。抑制在 FcγRIIIb 下游激活的转化生长因子-β 激活激酶 1 (TAK1)，可以以与纤维尺寸无关的方式显着减少 NET 的释放。这些结果表明，体外电纺生物材料诱导的 NET 释放很大程度上受到 IgG 吸附、FcγRIIIb 的结合以及通过 TAK1 的信号传导的调节。通过避免 NET 的不利影响并增加原位组织再生的潜力，对该途径的调节可能对调节中性粒细胞介导的炎症产生有益的治疗效果。
During the acute inflammatory response, the release of neutrophil extracellular traps (NETs) is a pro-inflammatory, preconditioning event on a biomaterial surface. Therefore, regulation of NET release through biomaterial design is one strategy to enhance biomaterial-guided in situ tissue regeneration. In this study, IgG adsorption on electrospun polydioxanone biomaterials with differing fiber sizes was explored as a regulator of in vitro human neutrophil NET release. The propensity to release NETs was increased and decreased by modulating adsorbed IgG, suggesting a functional link between IgG and NET formation. Fiber-size dependent NET release was reduced by blocking FcγRIIIb, but not FcγRI, FcγRIIa, or Mac-1 (CD11b/CD18), indicating a specific receptor mediated neutrophil response. Inhibition of transforming growth factor-β-activated kinase 1 (TAK1), which is activated downstream of FcγRIIIb, significantly reduced the release of NETs in a fiber size-independent manner. These results indicate that in vitro electrospun biomaterial-induced NET release is largely regulated by IgG adsorption, engagement of FcγRIIIb, and signaling through TAK1. Modulation of this pathway may have beneficial therapeutic effects for regulating neutrophil-mediated inflammation by avoiding the adverse effects of NETs and increasing the potential for in situ tissue regeneration.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
20.3
作者：
Chen, Kan;Nishi, Hiroshi;Mayadas, Tanya N.
通讯作者：
Mayadas, Tanya N.
影响因子：
15.9
作者：
GUYRE, PM;CAMPBELL, AS;FANGER, MW
通讯作者：
FANGER, MW
影响因子：
4.6
作者：
Fetz, Allison E.;Fantaziu, Cristina A.;Bowlin, Gary L.
通讯作者：
Bowlin, Gary L.
影响因子：
4.1
作者：
Fetz, Allison E.;Neeli, Indira;Bowlin, Gary L.
通讯作者：
Bowlin, Gary L.