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1、MedicinalChemistry,2007,3,13-2013BiophysicalCharacterizationoftheInteractionofEndotoxinswithHemo-globins11123JörgHowe,MalteHammer,ChristianAlexander,ManfredRössle,KarinFournier,3451Jean-PierreMach,ThierryWaelli,ReginaldM.Gorczynski,ArturJ.Ulmer,111,*UlrichZähringer,ErnstTh.Rietscheland
2、KlausBrandenburg12PPForschungszentrumBorstel,Leibniz-ZentrumfürMedizinundBiowissenschaften,Borstel,Germany;EuropeanMo-3lecularBiologyLaboratory,Hamburg,Germany;InstitutedeBiochemie,UniversitédeLausanne,Lausanne,Switzer-45land;CliniqueLaPrairie,Montreux,Switzerland;Dep.ofSurgeryandImmun
3、ology,UniversityHealthNetwork,To-ronto,CanadaAbstract:Bacterialendotoxin(lipopolysaccharide,LPS)isthemajorcomponentoftheouterleafletoftheoutermem-braneinGram-negativebacteria.Duringsevereinfections,bacteriamayreachthebloodcircuitofhumans,andendotox-insmaybereleasedfromthebacteriaduetoc
4、elldivisionorcelldeath.InparticularenterobacterialformsofLPSrepre-sentextremelystrongactivatormoleculesofthehumanimmunesystemcausingarapidinductionofcytokineproductioninmonocytesandmacrophages.VariousmammalianbloodproteinshavebeendocumentedtodisplayLPSbindingactivi-tiesmediatingnormall
5、ydecreasingeffectsinthebiologicalactivityofLPS.Inmorerecentstudies,theessentialsystemicoxygentransportationproteinhemoglobin(Hb)hasbeenshowntoamplifyLPS-inducedcytokineproductiononimmunecells.Themechanismresponsibleforthiseffectispoorlyunderstood.Here,wecharacterizetheinteractionofhemo
6、globinwithLPSbyusingbiophysicalmethods.Thedatapresented,reveal-ingthechangesofthetypeandsizeofsupramolecularaggregatesofLPSinthepresenceofHb,allowabetterunderstand-ingofthehemoglobin-inducedincreaseinbioactivityofLPS.INTRODUCTIONaddition,lowerconcentrationsofcell-freeHbareconstantlyrel
7、easedintothecirculationduetoaninherentintravascularBacterialendotoxin(lipopolysaccharide,LPS),withitshemolyticdisruptionoferythrocyteswhichcanbelargelyhydrophobicmembraneanchorlipidAconstitutesthemajorincreasedduringthecourseofsevereanemichemoglobi-lipidcomponentoftheoutermembraneofG
