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增加人工黏液的黏弹性并降低其可输送性。

increases viscoelasticity and decreases transportability of artificial mucus.

作者信息

Costello Caitlin, Murphree-Terry Mikayla, Oden Ashley, Combs Sarah, Keith John, Birket Susan

机构信息

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.

出版信息

iScience. 2025 Aug 5;28(9):113265. doi: 10.1016/j.isci.2025.113265. eCollection 2025 Sep 19.

Abstract

Muco-obstructive lung diseases presenting with mucin hyperconcentration can have increased viscoelasticity that prevents the mucus in the airways from being easily transported and that is prone to infection from opportunistic pathogens including (PA). The direct role that PA may have on decreasing mucus transportability has not yet been determined. In this study, PA was found to increase the viscosity and elasticity of artificial mucus replicating early and intermediate stages of muco-obstructive lung disease and reduce mucus transportability. Evaluation of how PA could be altering the mucus determined that PA degrades mucins with a metalloproteinase. Supernatant fractionation of PA determined that the potential mucinase was >100 kDa and therefore larger than previously identified PA metalloproteinases. Our study provides explanation as to why PA is detrimental to the progression of muco-obstructive lung disease by presenting its ability to actively impede mucus transport through mucin degradation and viscoelastic changes.

摘要

呈现粘蛋白高浓度的粘液阻塞性肺部疾病,其粘弹性可能增加,这会阻碍气道中的粘液被轻易运输,并且容易受到包括铜绿假单胞菌(PA)在内的机会性病原体感染。PA对降低粘液运输能力可能具有的直接作用尚未确定。在本研究中,发现PA会增加模拟粘液阻塞性肺病早期和中期的人工粘液的粘度和弹性,并降低粘液运输能力。对PA如何改变粘液的评估确定,PA通过一种金属蛋白酶降解粘蛋白。对PA的上清液分级分离确定,潜在的粘蛋白酶分子量大于100 kDa,因此比先前鉴定的PA金属蛋白酶更大。我们的研究通过展示PA通过粘蛋白降解和粘弹性变化积极阻碍粘液运输的能力,解释了为什么PA对粘液阻塞性肺病的进展有害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a786/12362397/0a32319ba0ef/fx1.jpg

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