Electrospun Polydioxanone Loaded With Chloroquine Modulates Template-Induced NET Release and Inflammatory Responses From Human Neutrophils.
Electrospun Polydioxanone Loaded With Chloroquine Modulates Template-Induced NET Release and Inflammatory Responses From Human Neutrophils.
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带有氯喹调节的静电播种聚二氧烷酮诱导的净释放和人类嗜中性粒细胞的炎症反应。
DOI：
10.3389/fbioe.2021.652055
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发表时间：
2021
影响因子：
5.7
通讯作者：
Bowlin GL
中科院分区：
文献类型：
--
作者：
Fetz AE;Wallace SE;Bowlin GL
生物材料的植入迅速启动组织修复程序，最初以中性粒细胞涌入为特征。在急性炎症反应中，中性粒细胞释放中性粒细胞胞外陷阱（NETs）并分泌可溶性信号来调节组织环境。在这项工作中，我们评估了二磷酸氯喹，一种具有免疫调节和抗血栓作用的抗疟疾药物，作为一种电纺丝生物材料添加剂来调节中性粒细胞介导的炎症。优化聚二氧环酮的静电纺丝，在1 h内快速洗脱氯喹，并在体外3和6 h与新鲜人外周血中性粒细胞评估急性中性粒细胞与生物材料的相互作用，然后量化NETs的释放以及炎症和再生因子的分泌。我们的研究结果表明，氯喹在早期时间点以生物材料表面积依赖的方式抑制NET释放，而在早期和晚期时间点调节信号分泌。更具体地说，氯喹洗脱下调了白细胞介素8 （IL-8）和基质金属蛋白酶9的分泌，同时上调了肝细胞生长因子、血管内皮生长因子A和IL-22的分泌，表明可能向中性粒细胞表型的解决转变。因此，我们将氯喹作为生物材料添加剂的新用途可能具有协同作用，免疫调节作用，有利于生物材料引导的原位组织再生应用。
The implantation of a biomaterial quickly initiates a tissue repair program initially characterized by a neutrophil influx. During the acute inflammatory response, neutrophils release neutrophil extracellular traps (NETs) and secrete soluble signals to modulate the tissue environment. In this work, we evaluated chloroquine diphosphate, an antimalarial with immunomodulatory and antithrombotic effects, as an electrospun biomaterial additive to regulate neutrophil-mediated inflammation. Electrospinning of polydioxanone was optimized for rapid chloroquine elution within 1 h, and acute neutrophil-biomaterial interactions were evaluated in vitro with fresh human peripheral blood neutrophils at 3 and 6 h before quantifying the release of NETs and secretion of inflammatory and regenerative factors. Our results indicate that chloroquine suppresses NET release in a biomaterial surface area–dependent manner at the early time point, whereas it modulates signal secretion at both early and late time points. More specifically, chloroquine elution down-regulates interleukin 8 (IL-8) and matrix metalloproteinase nine secretion while up-regulating hepatocyte growth factor, vascular endothelial growth factor A, and IL-22 secretion, suggesting a potential shift toward a resolving neutrophil phenotype. Our novel repurposing of chloroquine as a biomaterial additive may therefore have synergistic, immunomodulatory effects that are advantageous for biomaterial-guided in situ tissue regeneration applications.
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影响因子：
20.3
作者：
Christoffersson, Gustaf;Vagesjo, Evelina;Phillipson, Mia
通讯作者：
Phillipson, Mia
DOI：
10.4049/jimmunol.1501541
发表时间：
2016-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen F;Cao A;Yao S;Evans-Marin HL;Liu H;Wu W;Carlsen ED;Dann SM;Soong L;Sun J;Zhao Q;Cong Y
通讯作者：
Cong Y
影响因子：
5.5
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
通讯作者：
Rainger, G. Ed
影响因子：
5.5
作者：
Christoffersson, Gustaf;Lomei, Jalal;Phillipson, Mia
通讯作者：
Phillipson, Mia
影响因子：
7.3
作者：
Degroote, Roxane L.;Weigand, Maria;Deeg, Cornelia A.
通讯作者：
Deeg, Cornelia A.