BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance

Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is...

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Bibliographic Details
Published in:	American journal of physiology. Lung cellular and molecular physiology Vol. 325; no. 6; p. L765
Main Authors:	Donoghue, Lauren J, Markovetz, Matthew R, Morrison, Cameron B, Chen, Gang, McFadden, Kathryn M, Sadritabrizi, Taraneh, Gutay, Mark I, Kato, Takafumi, Rogers, Troy D, Snead, Jazmin Y, Livraghi-Butrico, Alessandra, Button, Brian, Ehre, Camille, Grubb, Barbara R, Hill, David B, Kelada, Samir N P
Format:	Journal Article
Language:	English
Published:	United States 01-12-2023
Subjects:	Animals Humans Lung Diseases - metabolism Mice Mice, Knockout Mucociliary Clearance - physiology Mucus - metabolism Respiratory System - metabolism mucociliary clearance rheology mucin viscoelasticity mucus
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Summary:	Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the gene as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using knockout (KO) mice. Reduced MCC in KO mice occurred in the absence of defects in epithelial ion transport or reduced ciliary beat frequency. Loss of BPIFB1 in vivo and in vitro altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and the protein mesh of secreted mucus in human airway epithelia cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network. BPIFB1, also known as LPLUNC1, was found to regulate mucociliary clearance (MCC), a key aspect of host defense in the airway. Loss of this protein was also associated with altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC.
ISSN:	1522-1504
DOI:	10.1152/ajplung.00390.2022