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Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways.

Abstract：

:Mucus, with its burden of inspired particulates and pathogens, is cleared from mucosal surfaces of the airways by cilia beating within the periciliary layer (PCL). The PCL is held to be "watery" and free of mucus by thixotropic-like forces arising from beating cilia. With radii of gyration ~250 nm, however, polymeric mucins should reptate readily into the PCL, so we assessed the glycocalyx for barrier functions. The PCL stained negative for MUC5AC and MUC5B, but it was positive for keratan sulfate (KS), a glycosaminoglycan commonly associated with glycoconjugates. Shotgun proteomics showed KS-rich fractions from mucus containing abundant tethered mucins, MUC1, MUC4, and MUC16, but no proteoglycans. Immuno-histology by light and electron microscopy localized MUC1 to microvilli, MUC4 and MUC20 to cilia, and MUC16 to goblet cells. Electron and atomic force microscopy revealed molecular lengths of 190-1,500 nm for tethered mucins, and a finely textured glycocalyx matrix filling interciliary spaces. Adenoviral particles were excluded from glycocalyx of the microvilli, whereas the smaller adenoassociated virus penetrated, but were trapped within. Hence, tethered mucins organized as a space-filling glycocalyx function as a selective barrier for the PCL, broadening their role in innate lung defense and offering new molecular targets for conventional and gene therapies.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Kesimer M,Ehre C,Burns KA,Davis CW,Sheehan JK,Pickles RJ

doi

10.1038/mi.2012.81

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

379-92

issue

2

eissn

1933-0219

issn

1935-3456

pii

mi201281

journal_volume

6

pub_type

杂志文章

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