Amplification of P. falciparum Cytoadherence through Induction of a Pro-Adhesive State in Host Endothelium 英文参考文献.docVIP
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Amplification of P. falciparum Cytoadherence through Induction of a Pro-Adhesive State in Host Endothelium 英文参考文献
AmplificationofP.falciparumCytoadherencethrough
InductionofaPro-AdhesiveStateinHostEndothelium
YangWu1,TadgeSzestak1,MoniqueStins2,AlisterG.Craig1*
1LiverpoolSchoolofTropicalMedicine,Liverpool,UnitedKingdom,2RTJohnsonDivisionofNeuroImmunology,JohnsHopkinsSchoolofMedicine,Baltimore,Maryland,
UnitedStatesofAmerica
Abstract
ThisstudyexaminedtheabilityofP.falciparum-infectederythrocytes(IE)toinduceapro-adhesiveenvironmentinthehost
endotheliumduringmalariainfection,priortothesystemiccytokineactivationseeninthelaterphaseofdisease.Previous
work had shown increases in receptor levels but had not measured to actual impact on IE binding. Using a co-culture
system with a range of endothelial cells (EC) and IE with different cytoadherent properties, we have characterised the
specificexpressionofadhesionreceptorsandsubsequentIEbindingbyFACSandadhesionassays.Wehavealsoexamined
the specific signalling pathways induced during co-culture that are potentially involved in the induction of receptor
expression.TheresultsconfirmedthatICAM-1isup-regulated,albeitatmuchlowerlevelsthanseenwithTNFactivation,in
responsetoco-culturewithinfectederythrocytesinallthreetissueendothelialcelltypestestedbutthatup-regulationof
VCAM-1istissue-dependent.ThissmallincreaseinthelevelsofECreceptorscorrelatedwithlargechangesinIEadhesion
ability. Co-culture with either RBC or IE increased the potential of subsequent adhesion indicating priming/modulation
effectsonECwhichmakethemmoresusceptibletoadhesionandtherebytherecruitmentofIE.Trypsinsurfacedigestionof
IEandtheuseofaPfsbp1-knockout(ko)parasitelineabrogatedtheup-regulationofICAM-1andreducedIEbindingtoEC
suggestingthatPfEMP-1andothermoleculesexportedtotheIEsurfaceviathePfSBP1pathwayaremajormediatorsofthis
phenotype.ThiswasalsosupportedbythehigherinductionofECadhesionreceptorsbyadherentIEcomparedtoisogenic,
non-adherentlines.
Citation: Wu Y, Szestak T, Stins M, Craig AG (2011) Amplification of P. falciparum Cytoadherence through Induction of a Pro-Adhesive
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