Nanoparticle-Induced Augmentation of Neutrophils' Phagocytosis of Bacteria.
Nanoparticle-Induced Augmentation of Neutrophils' Phagocytosis of Bacteria.
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DOI：
10.3389/fphar.2022.923814
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发表时间：
2022
影响因子：
5.6
通讯作者：
Brenner, Jacob S.
中科院分区：
文献类型：
--
作者：
Rubey, Kathryn M.;Mukhitov, Alexander R.;Nong, Jia;Wu, Jichuan;Krymskaya, Vera P.;Myerson, Jacob W.;Worthen, G. Scott;Brenner, Jacob S.
尽管抗生素的力量，细菌感染仍然是一个主要的杀手，由于抗生素耐药性和宿主免疫系统失调。我们和其他人一直在开发载药纳米颗粒，通过中性粒细胞（细菌感染中的第一反应白细胞）的工程向性，将其定位于感染和炎症部位。在这里，我们研究了一个成员的一个广泛的类嗜中性粒细胞的纳米粒子如何影响中性粒细胞的行为，特别是质疑纳米粒子是否减弱一个重要的功能，细菌吞噬。我们发现这些纳米颗粒实际上增加了非调理细菌的吞噬作用，使其增加了50%。我们发现这种吞噬作用的增强可能是一种进化的反应，因为调理细菌也增强了非调理细菌的吞噬作用。增强非调理素化细菌的吞噬作用可以证明在两种临床情况下特别有益：在低补体血症患者中（意味着在诸如新生儿败血症和肝衰竭的病症中观察到的主要细菌调理素、补体蛋白的低水平）或对于在很大程度上抵抗补体调理作用的细菌（例如，奈瑟菌属）。此外，我们注意到，1）先前用细菌处理增强嗜中性粒细胞对嗜中性粒细胞纳米颗粒的摄取; 2）嗜中性粒细胞纳米颗粒与嗜中性粒细胞内的细菌共定位。嗜中性粒细胞纳米颗粒增强嗜中性粒细胞吞噬作用并与嗜中性粒细胞内的细菌一起定位的观察表明，这些纳米颗粒将用作改善细菌疾病的药物的有用载体。
Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of infection and inflammation via engineered tropism for neutrophils, the first-responder leukocytes in bacterial infections. Here, we examined how a member of a broad class of neutrophil-tropic nanoparticles affects neutrophil behavior, specifically questioning whether the nanoparticles attenuate an important function, bacterial phagocytosis. We found these nanoparticles actually augment phagocytosis of non-opsonized bacteria, increasing it by ∼50%. We showed this augmentation of phagocytosis is likely co-opting an evolved response, as opsonized bacteria also augment phagocytosis of non-opsonized bacteria. Enhancing phagocytosis of non-opsonized bacteria may prove particularly beneficial in two clinical situations: in hypocomplementemic patients (meaning low levels of the main bacterial opsonins, complement proteins, seen in conditions such as neonatal sepsis and liver failure) or for bacteria that are largely resistant to complement opsonization (e.g., Neisseria). Additionally, we observe that; 1) prior treatment with bacteria augments neutrophil uptake of neutrophil-tropic nanoparticles; 2) neutrophil-tropic nanoparticles colocalize with bacteria inside of neutrophils. The observation that neutrophil-tropic nanoparticles enhance neutrophil phagocytosis and localize with bacteria inside neutrophils suggests that these nanoparticles will serve as useful carriers for drugs to ameliorate bacterial diseases.
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影响因子：
3.7
作者：
Ferrer MC;Shuvaev VV;Zern BJ;Composto RJ;Muzykantov VR;Eckmann DM
通讯作者：
Eckmann DM
眼镜蛇毒因子诱导的补体耗竭通过减轻血气屏障损伤来预防肺缺血再灌注损伤
影响因子：
4.6
作者：
Haihua C;Wei W;Kun H;Yuanli L;Fei L
通讯作者：
Fei L
影响因子：
0.2
作者：
Parasuraman S;Raveendran R;Kesavan R
通讯作者：
Kesavan R
影响因子：
5.5
作者：
Brekke, Ole-Lars;Christiansen, Dorte;Mollnes, Tom E.
通讯作者：
Mollnes, Tom E.
影响因子：
3.2
作者：
Moraes, TJ;Zurawska, JH;Downey, GP
通讯作者：
Downey, GP