Abstract
Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.
Highlights
The airways are constantly challenged by inhaled microbial pathogens
Measure of nasal mucociliary transport rate (NMTR) using microCT-SPECT albumin macroagregates marked with technetium 99 metastable (Tc99m)
We observed that T2R agonists increased Mucociliary clearance (MCC) in vivo by a combined mechanism including the increase of ciliary beat frequency (CBF) of epithelial ciliated cells and bronchodilation
Summary
The airways are constantly challenged by inhaled microbial pathogens. Mucociliary clearance (MCC) is the primary physical defense against inhaled pathogens, toxins and particulates in the respiratory system. Appropriate mucus production and coordinated ciliary activity are the premises for effective clearance. Micro-CT-SPECT Mucociliary Function Analysis of Bitter Taste Agonists In Vivo. 2014-fe2a818ac5) and centro de investigaciones biomedicas en red de enfermedades respiratorias (CIBERES; CB06/06/0027; http://www.ciberes.org/ ), TRACE (TRA2009-0311; (https://www.boe.es/ boe/dias/2010/08/05/pdfs/BOE-A-2010-12605.pdf) as well as by fondos de la Generalitat Valenciana Prometeo II/2013/014 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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