Diffusion of macromolecules and virus-like particles in human cervical mucus

Diffusion of macromolecules and virus-like particles in human cervical mucus
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DOI:
10.1016/s0006-3495(01)75844-4
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发表时间:
2001-10-01
影响因子:
3.4
通讯作者:
Cone, RA
Cone, RA
中科院分区:
生物学3区
文献类型:
--
作者:
Olmsted, SS;Padgett, JL;Cone, RA

文献摘要

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为了确定大分子和病毒是否可以通过粘液扩散,我们观察了蛋白质,微球和病毒在新鲜的人宫颈粘液样品中的运动,使用光漂白后的荧光恢复和多重图像摄影。两种衣壳病毒样颗粒,人乳头瘤病毒(55 nm,类似于20,000 kDa)和诺瓦克病毒(38 nm,类似于10,000 kDa),以及大多数测试的球状蛋白(15-650 kDa)在粘液中扩散的速度与在盐水中一样快。宫颈粘液的电子显微镜检查证实,粘蛋白纤维之间的网格间距足够大(20-200 nm),使小病毒基本上不受阻碍地通过粘液扩散。相反,单纯疱疹病毒(180 nm)与粘稠粘液链共定位,表明单纯疱疹病毒与衣壳病毒颗粒不同,与粘蛋白形成低亲和力结合。聚苯乙烯微球(59-1000 nm)与粘蛋白的结合更紧密,将它们捆绑成粗电缆。虽然免疫球蛋白太小而不能被粘蛋白之间的网格间距减慢,但IgM的扩散被粘液减慢。IgM-Fc(5 μ)的扩散被粘液缓慢地减慢,IgM-Fc(5 μ)是除去所有10个Fab部分的IgM的Fc五聚体核心。这表明抗体的Fc部分与粘蛋白形成低亲和力键。
To determine whether or not large macromolecules and viruses can diffuse through mucus, we observed the motion of proteins, microspheres, and viruses in fresh samples of human cervical mucus using fluorescent recovery after photobleaching and multiple image photography. Two capsid virus-like particles, human papilloma virus (55 nm, similar to 20,000 kDa) and Norwalk virus (38 nm, similar to 10,000 kDa), as well as most of the globular proteins tested (15-650 kDa) diffused as rapidly in mucus as in saline. Electron microscopy of cervical mucus confirmed that the mesh spacing between mucin fibers is large enough (20-200 nm) for small viruses to diffuse essentially unhindered through mucus. In contrast, herpes simplex virus (180 nm) colocalized with strands of thick mucus, suggesting that herpes simplex virus, unlike the capsid virus particles, makes low-affinity bonds with mucins. Polystyrene microspheres (59-1000 nm) bound more tightly to mucins, bundling them into thick cables. Although immunoglobulins are too small to be slowed by the mesh spacing between mucins, diffusion by IgM was slowed by mucus. Diffusion by IgM-Fc(5 mu), the Fc pentamer core of an IgM with all 10 Fab moieties removed, was comparably slowed by mucus. This suggests that the Fc moieties of antibodies make low-affinity bonds with mucins.