Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity.
Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity.
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DOI：
10.1080/10717544.2018.1477860
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Maruyama T
中科院分区：
文献类型：
--
作者：
Taguchi K;Nagao S;Maeda H;Yanagisawa H;Sakai H;Yamasaki K;Wakayama T;Watanabe H;Otagiri M;Maruyama T
巨噬细胞在各种炎症性疾病中起核心作用，并大致分为两个亚群，M1和M2巨噬细胞。在急性炎症性疾病的愈合过程中，将M1巨噬细胞的产生转移到M2巨噬细胞是可取的，因为M1巨噬细胞分泌促炎细胞因子，而M2种类分泌抗炎细胞因子。以前的研究结果表明，当巨噬细胞用一氧化碳（CO）处理时，抗炎细胞因子的分泌增加，促炎细胞因子的表达受到抑制，这表明CO可能具有调节巨噬细胞向M2样表型产生的潜力。在这项研究中，我们研究了使用基于纳米技术的CO供体，即CO结合的血红蛋白囊泡（CO-HbV）的CO靶向巨噬细胞是否调节其极化并显示出对炎症性疾病的治疗作用。结果显示，CO-HbV处理使巨噬细胞系向M2样表型极化。此外，在使用急性胰腺炎模型小鼠作为炎性疾病模型的体内研究中，CO-HbV治疗也倾向于使巨噬细胞向M2样表型转化，并抑制胰腺中的嗜中性粒细胞浸润，导致显著的炎症。除了抑制急性胰腺炎外，CO-HbV还减少了随后的胰腺炎相关急性肺损伤。这可能是由于抑制了全身性炎症、肺中的中性粒细胞浸润和HMGB-1的产生。这些发现表明，CO-HbV通过调节巨噬细胞和中性粒细胞活性对炎性疾病发挥上级抗炎作用。
Macrophages play a central role in various inflammatory disorders and are broadly divided into two subpopulations, M1 and M2 macrophage. In the healing process in acute inflammatory disorders, shifting the production of M1 macrophages to M2 macrophages is desirable, because M1 macrophages secrete pro-inflammatory cytokines, whilst the M2 variety secrete anti-inflammatory cytokines. Previous findings indicate that when macrophages are treated with carbon monoxide (CO), the secretion of anti-inflammatory cytokine is increased and the expression of pro-inflammatory cytokines is inhibited, indicating that CO may have a potential to modulate the production of macrophages toward the M2-like phenotype. In this study, we examined the issue of whether CO targeting macrophages using a nanotechnology-based CO donor, namely CO-bound hemoglobin vesicles (CO-HbV), modulates their polarization and show therapeutic effects against inflammatory disorders. The results showed that the CO-HbV treatment polarized a macrophage cell line toward an M2-like phenotype. Furthermore, in an in vivo study using acute pancreatitis model mice as a model of an inflammatory disease, a CO-HbV treatment also tended to polarize macrophages toward an M2-like phenotype and inhibited neutrophil infiltration in the pancreas, resulting in a significant inflammation. In addition to the suppression of acute pancreatitis, CO-HbV diminished a subsequent pancreatitis-associated acute lung injury. This could be due to the inhibition of the systemic inflammation, neutrophil infiltration in the lungs and the production of HMGB-1. These findings suggest that CO-HbV exerts superior anti-inflammatory effects against inflammatory disorders via the regulation of macrophage and neutrophil activity.
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DOI：
10.1016/j.jconrel.2016.01.026
发表时间：
2016-10-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
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通讯作者：
Khademhosseini A
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2.8
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影响因子：
5.8
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