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健康及黏液阻塞性疾病中人体气道黏液的水吸附与结构特性

Water Sorption and Structural Properties of Human Airway Mucus in Health and Muco-Obstructive Diseases.

作者信息

Kelly Susyn J, Genevskiy Vladislav, Björklund Sebastian, Gonzalez-Martinez Juan F, Poeschke Lara, Schröder Maik, Nilius Georg, Tatkov Stanislav, Kocherbitov Vitaly

机构信息

Fisher & Paykel Healthcare Ltd., 15 Maurice Paykel Place, East Tamaki, Auckland NZ-2013, New Zealand.

Department of Clinical Sciences, Ross University of Veterinary Medicine, Basseterre KN-0101, Saint Kitts and Nevis.

出版信息

Biomacromolecules. 2024 Mar 11;25(3):1578-1591. doi: 10.1021/acs.biomac.3c01170. Epub 2024 Feb 9.

DOI:10.1021/acs.biomac.3c01170
PMID:38333985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10934264/
Abstract

Muco-obstructive diseases change airway mucus properties, impairing mucociliary transport and increasing the likelihood of infections. To investigate the sorption properties and nanostructures of mucus in health and disease, we investigated mucus samples from patients and cell cultures (cc) from healthy, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) airways. Atomic force microscopy (AFM) revealed mucin monomers with typical barbell structures, where the globule to spacer volume ratio was the highest for CF mucin. Accordingly, synchrotron small-angle X-ray scattering (SAXS) revealed more pronounced scattering from CF mucin globules and suggested shorter carbohydrate side chains in CF mucin and longer side chains in COPD mucin. Quartz crystal microbalance with dissipation (QCM-D) analysis presented water sorption isotherms of the three types of human airway mucus, where, at high relative humidity, COPD mucus had the highest water content compared to cc-CF and healthy airway mucus (HAM). The higher hydration of the COPD mucus is consistent with the observation of longer side chains of the COPD mucins. At low humidity, no dehydration-induced glass transition was observed in healthy and diseased mucus, suggesting mucus remained in a rubbery state. However, in dialyzed cc-HAM, a sorption-desorption hysteresis (typically observed in the glassy state) appeared, suggesting that small molecules present in mucus suppress the glass transition.

摘要

黏液阻塞性疾病会改变气道黏液特性,损害黏液纤毛运输功能,并增加感染的可能性。为了研究健康和患病状态下黏液的吸附特性和纳米结构,我们研究了来自患者的黏液样本以及来自健康、慢性阻塞性肺疾病(COPD)和囊性纤维化(CF)气道的细胞培养物(cc)。原子力显微镜(AFM)显示黏蛋白单体具有典型的杠铃结构,其中CF黏蛋白的球状体与间隔物体积比最高。相应地,同步加速器小角X射线散射(SAXS)显示CF黏蛋白球状体的散射更明显,并表明CF黏蛋白中的碳水化合物侧链较短,而COPD黏蛋白中的侧链较长。石英晶体微天平与耗散(QCM-D)分析给出了三种类型的人气道黏液的水吸附等温线,其中在高相对湿度下,与cc-CF和健康气道黏液(HAM)相比,COPD黏液的含水量最高。COPD黏液较高的水合作用与观察到的COPD黏蛋白较长的侧链一致。在低湿度下,在健康和患病的黏液中未观察到脱水诱导的玻璃化转变,表明黏液保持橡胶态。然而,在透析后的cc-HAM中,出现了吸附-解吸滞后现象(通常在玻璃态中观察到),这表明黏液中存在的小分子抑制了玻璃化转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecc9/10934264/57aed3c26f84/bm3c01170_0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecc9/10934264/57aed3c26f84/bm3c01170_0009.jpg

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本文引用的文献

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Sci Transl Med. 2023 Jun 7;15(699):eabo7728. doi: 10.1126/scitranslmed.abo7728.
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Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease.气道阻塞性黏液栓与慢性阻塞性肺疾病患者的死亡率。
JAMA. 2023 Jun 6;329(21):1832-1839. doi: 10.1001/jama.2023.2065.
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Rapid Viscoelastic Characterization of Airway Mucus Using a Benchtop Rheometer.
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Variability in tracheal mucociliary transport is not controlled by beating cilia in lambs in vivo during ventilation with humidified and nonhumidified air.在体内通气时,用加湿和未加湿的空气对羔羊进行通气,不会控制气管纤毛粘液传输的可变性。
Am J Physiol Lung Cell Mol Physiol. 2021 Apr 1;320(4):L473-L485. doi: 10.1152/ajplung.00485.2020. Epub 2021 Jan 13.
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Mucus, mucins, and cystic fibrosis.黏液、黏蛋白和囊性纤维化。
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