Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation.docVIP

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Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation.doc

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Cigarette Smoke-Induced Collagen Destruction; Key to Chronic Neutrophilic Airway Inflammation

CigaretteSmoke-InducedCollagenDestruction;Keyto ChronicNeutrophilicAirwayInflammation? SaskiaA.Overbeek1,SaskiaBraber1,PimJ.Koelink1,PaulA.J.Henricks1,EsmaeilMortaz1,2, AdeleT.LoTamLoi3,PatriciaL.Jackson4,JohanGarssen1,5,GerryT.M.Wagenaar6,WimTimens7, LeoKoenderman2,J.EdwinBlalock3,AlettaD.Kraneveld1,GertFolkerts1* 1DivisionofPharmacology,UtrechtInstituteforPharmaceuticalSciences,FacultyofScience,UtrechtUniversity,Utrecht,TheNetherlands,2ChronicRespiratoryDisease Researchcenter,NationalResearchInstituteofTuberculosisandlungdisease(NRITLD),MasihDaneshvariHospital,ShahidBeheshtiUniversityofMedicalsciences,Tehran, Iran,3DepartmentofRespiratoryMedicine,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands,4DivisionofPulmonary,AllergyandCriticalCareMedicineand UABLungHealthCenter,DepartmentofMedicine,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,5DanoneResearch–Centrefor Specialised Nutrition, Wageningen, The Netherlands, 6Department of Pediatrics,Division of Neonatology,Leiden University Medical Center, Leiden, The Netherlands, 7DepartmentofPathologyandMedicalBiology,UniversityMedicalCenterGroningen,Groningen,TheNetherlands Abstract Background:Cigarettesmokinginducesinflammatoryresponsesinallsmokersandisthemajorriskfactorforlungdisease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline(N-ac-PGP).Thegenerationofthistripeptideismediatedbyamultisteppathwayinvolvingmatrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE). Here we investigated whether cigarette smoke extract (CSE)stimulateshumanPMNstobreakdownwholematrixcollagenleadingtothegenerationofthechemotacticcollagen fragmentN-ac-PGP. Methodology/PrincipalFindings:IncubatingPMNswithCSEledtothereleaseofchemo-attractantCXCL8andproteases MMP8 and MMP9. PMNs constitutively expr