Antiphospholipid Antibodies Bind ATP A putative Mechanism for the Pathogenesis of Neuronal Dysfunction英文文献资料.docVIP

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Antiphospholipid Antibodies Bind ATP A putative Mechanism for the Pathogenesis of Neuronal Dysfunction英文文献资料.doc

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Antiphospholipid Antibodies Bind ATP A putative Mechanism for the Pathogenesis of Neuronal Dysfunction英文文献资料

ClinicalDevelopmentalImmunology,September2005;12(3):175–180 AntiphospholipidantibodiesbindATP:Aputativemechanism forthepathogenesisofneuronaldysfunction J.CHAPMAN1,2,3,L.SOLOVEICHICK1,S.SHAVIT1,Y.SHOENFELD4,A.D.KORCZYN1,2 1DepartmentofPhysiologyandPharmacology,SacklerFacultyofMedicine,TelAvivUniversity,RamatAviv69978,Israel, 2DepartmentofNeurology,SacklerFacultyofMedicine,TelAvivUniversity,RamatAviv69978,Israel, 3Departmentof Biochemistry,SacklerFacultyofMedicine,TelAvivUniversity,RamatAviv69978,Israel,and4DepartmentofMedicineBand ResearchUnitofAutoimmuneDiseases,ShebaMedicalCenter,TelHashomer,Israel Abstract Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibilitythataPLIgGfromhumansubjectsbindtoATPbyaf?nitycolumnandanenzymelinkedimmunosorbentassay (ELISA).SerawithhighlevelsofaPLIgGwerecollectedfrom12patientswiththeantiphospholipidsyndrome(APS).IgG fractionsfrom10of12APSpatientscontainedaPLthatcouldbeaf?nity-boundtoanATPcolumnandcompletelyeluted withNaCl 0.5M.A signi?cant(.50%)inhibitionof aPLIgGbindingbyATP 5mM wasfoundin themajority.Similar inhibitionwasobtainedwithADPbutnotwithAMPorcAMP.Alltheaf?nitypuri?edanti-ATPantibodiesalsoboundb2- glycoprotein-I (b2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding dependsonthisserumcofactor.Wefurther investigatedthispossibilityandfoundthatthebindingofb2-GPItotheATP columnwassimilartothatofaPLIgGinthatmostwasreversedbyNaCl0.5M.Furthermore,additionofb2-GPItoaPLIgG signi?cantlyincreasedtheamountofaPLbindingtoanATPcolumn.WeconcludethataPLIgGbindATP,probablythrough b2-GPI.ThisbindingcouldinterferewiththenormalextracellularfunctionofATPandsimilarneurotransmitters. Keywords: Antiphospholipidantibodies,adenosinetriphosphate,af?nitycolumns,beta2-glycoprotein-I Introduction bindendothelialcells(DelPapaetal.1995,Dueymes etal.1996,Bordronetal.1998).Acrucialobservation has been that aPL, including