BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.

Airway mucociliary clearance (MCC) is required for host defense and 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 Bpifb1 as a regulator of the levels of MUC5B in the airways using genetic approaches. Here, we show that BPIFB1 is required for normal mucociliary clearance in vivo using Bpifb1 knockout (KO) mice. Reduced MCC in Bpifb1 KO mice occurred in the absence of defects in sodium or chloride ion transport or changes in ciliary beat frequency. We found that BPIFB1 loss resulted in airway mucus flakes with significantly increased complex viscosity, a key biophysical property of mucus known to impact MCC. Finally, BPIFB1 protein colocalized with MUC5B in secretory granules and was present in mucus on the airway surface. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and may be a key protein constituent of the mucus network.