6533b829fe1ef96bd128a4b4

RESEARCH PRODUCT

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists

Javier Milara PayáJavier MilaraJulio CortijoJulio CortijoJose Luis OrtizMiguel ArmengotDesamparados CompañCelia SanzCelia SanzEsteban J. MorcilloEsteban J. MorcilloAmparo Ortiz

subject

0301 basic medicinePathologyPhysiologyRespiratory Systemlcsh:MedicineSingle Photon Emission Computed TomographyPharmacologyBiochemistryDiagnostic RadiologyReceptors G-Protein-CoupledMathematical and Statistical Techniques0302 clinical medicineBronchodilationMedicine and Health Scienceslcsh:ScienceTomographyLungMammalsMultidisciplinaryRadiology and ImagingDrugsfood and beveragesChloroquineAnimal Modelsrespiratory systemPulmonary ImagingBody Fluidsmedicine.anatomical_structureMucociliary ClearanceVertebratesPhysical SciencesAnatomyStatistics (Mathematics)Research ArticleAgonistmedicine.medical_specialtySingle Photon Emission Computed Tomography Computed TomographyImaging TechniquesMucociliary clearancemedicine.drug_classGuinea PigsBronchiNeuroimagingResearch and Analysis MethodsRodentsGuinea pigAntimalarials03 medical and health sciencesModel OrganismsDiagnostic MedicineIn vivoAlbuminsmedicineAnimalsHumansStatistical MethodsPharmacologyAnalysis of VarianceLungbusiness.industrylcsh:ROrganismsBiology and Life SciencesProteinsX-Ray MicrotomographyMucus030104 developmental biology030228 respiratory systemAmniotesNanoparticleslcsh:QNasal administrationbusinessMathematicsEx vivoNeuroscience

description

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) microCT-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 microCT-SPECT analysis. The study was supported by the spanish goverment grants SAF2014-55322-P (JC; https://sede.micinn.gob.es/stfls/eSede/Ficheros/2015/Anexo_Preseleccionados_PRP_Proyectos_Excelencia_2014.pdf), SAF2015-65368-R (EM; https://sede.micinn.gob.es/stfls/eSede/Ficheros/2016/Anexo_Preseleccionados_Propuesta_Resolucion_Provisional_Proyectos_Retos_2015.pdf), FIS CP11/00293, FIS PI14/01733 (JM; http://gesdoc.isciii.es/?action=download&id=08/10/2014-fe2a818ac5) and centro de investigaciones biomédicas 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 (EM, JC, JM; http://www.cece.gva.es/poci/docs/2013/NUEVAS/RESOLUCIONES/PROMETEOII13_Resolucion_Concesion_c.pdf). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

yearjournalcountryeditionlanguage
2016-10-01
10.1371/journal.pone.0164399http://hdl.handle.net/10550/56938