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无菌性炎症改变了小鼠中性粒细胞的动力学。

Sterile inflammation alters neutrophil kinetics in mice.

机构信息

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bengaluru, India.

出版信息

J Leukoc Biol. 2022 Sep;112(3):395-409. doi: 10.1002/JLB.1A0321-132RR. Epub 2022 Feb 16.

Abstract

Neutrophils play a crucial role in establishing inflammation in response to an infection or injury, but their production rates, as well as blood and tissue residence times, remain poorly characterized under these conditions. Herein, using a biomaterial implant model to establish inflammation followed by in vivo tracking of newly formed neutrophils, we determine neutrophil kinetics under inflammatory conditions. To obtain quantifiable information from our experimental observations, we develop an ordinary differential equation-based mathematical model to extract kinetic parameters. Our data show that in the presence of inflammation resulting in emergency granulopoiesis-like conditions, neutrophil maturation time in the bone marrow reduces by around 60% and reduced half-life in the blood, compared with noninflammatory conditions. Additionally, neutrophil residence time at the inflammatory site increases by 2-fold. Together, these data improve our understanding of neutrophil kinetics under inflammatory conditions, which could pave the way for therapies that focus on modulating in vivo neutrophil dynamics.

摘要

中性粒细胞在感染或损伤后引发炎症反应中起着至关重要的作用,但在这些情况下,其生成率以及在血液和组织中的驻留时间仍未得到充分描述。在此,我们使用生物材料植入模型来建立炎症,然后对新形成的中性粒细胞进行体内跟踪,以确定炎症条件下的中性粒细胞动力学。为了从我们的实验观察中获得可量化的信息,我们开发了一个基于常微分方程的数学模型来提取动力学参数。我们的数据表明,在导致应急粒细胞生成样条件的炎症存在下,与非炎症条件相比,骨髓中中性粒细胞的成熟时间减少了约 60%,血液中的半衰期也缩短了。此外,中性粒细胞在炎症部位的驻留时间增加了两倍。这些数据共同提高了我们对炎症条件下中性粒细胞动力学的理解,这可能为专注于调节体内中性粒细胞动力学的治疗方法铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4349/7616002/2d5c36ef32bb/EMS196032-f009.jpg

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