Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-- and CFTRΔF508ΔF508 Pigs 英文参考文献.docVIP

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Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-- and CFTRΔF508ΔF508 Pigs 英文参考文献.doc

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Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-- and CFTRΔF508ΔF508 Pigs 英文参考文献

DefectiveFluidSecretionfromSubmucosalGlandsof NasalTurbinatesfromCFTR-/- andCFTRDF508/DF508 Pigs Hyung-JuCho*,NamSooJoo,JeffreyJ.Wine CysticFibrosisResearchLaboratory,PsychologyDepartment,StanfordUniversity,Stanford,California,UnitedStatesofAmerica Abstract Background:Cysticfibrosis(CF),causedbyreducedCFTRfunction,includesseveresinonasaldiseasewhichmaypredispose tolungdisease.NewlydevelopedCFpigsprovidemodelstostudytheonsetofCFpathophysiology.Weaskedifglands frompignasalturbinateshavesecretoryresponsessimilartothoseoftrachealglandsandifCFnasalglandsshowreduced fluidsecretion. Methodology/Principal Findings: Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, beingsmaller,morenumerous(densityperairwaysurfacearea),moresensitivetocarbachol,moresensitivetoforskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets(12CFand12controls)inresponsetoagonistswasmeasuredusingdigitalimagingofmucusbubblesformedunder oil.Secretionratesweresignificantlyreducedinallconditionstested.Fluidsecretoryrates(Controlsvs.CF,inpl/min/gland) wereasfollows:3mMforskolin: 9.262.2vs.0.660.3;1mMcarbachol:143.5635.5vs.52.2610.3;3mMforskolin +0.1mM carbachol: 25.865.8 vs. CF 4.560.9. We also compared CFDF508/DF508 with CFTR piglets and found significantly greater forskolin-stimulatedsecretionratesintheDF508vs.thenullpiglets(1.460.8,n=4vs.0.260.1,n=7).Anunexpectedage effectwasalsodiscovered:theratioofsecretionto3mMforskolinvs.1mMcarbacholwas,4timesgreaterinadultthanin neonatalnasalglands. -/- Conclusions/Significance: These findings reveal differences between nasal and tracheal glands, show defective fluid secretioninnasalglandsofCFpigs,revealsomesparedfunctionintheDF508vs.nullpiglets,andshowunexpectedage- dependentdifferences.Reducednasalglandfluidsecretionmaypredisposetosinonasalandlunginfections. Citation: ChoH-J,JooNS,WineJJ(2011)Defective FluidSecretionfromSubmucosalGlandso