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1、TheNewEnglandJournalofMedicineReviewArticlesMechanismsofDiseasea-andb-chemokines,whichcontainfourcysteines,appeartobethelargestfamilies.Inthea-chemo-kines,oneaminoacidseparatesthefirsttwocysteineFRANKLINH.EPSTEIN,M.D.,Editorresidues(cysteine–Xaminoaci
2、d–cysteine,orCXC),whereasintheb-chemokines,thefirsttwocysteineresiduesareadjacenttoeachother(cysteine–cys-CHEMOKINES—CHEMOTACTICteine,orCC)(Fig.1).Twochemokinesthatdonotfitintothisclassification,lymphotactin,9withonlyCYTOKINESTHATMEDIATEtwocysteines,a
3、ndfractalkine,10amembrane-boundINFLAMMATIONglycoproteininwhichthefirsttwocysteineresiduesareseparatedbythreeaminoacids(CXXXC)andtheANDREWD.LUSTER,M.D.,PH.D.chemokinedomainsitsonamucin-likestalk,mayrepresentadditionalfamilies.Thea-chemokinescanbefurthe
4、rsubdividedintothosethatcontainthesequenceglutamicacid–leu-HEattractionofleukocytestotissuesises-cine–arginineneartheNterminal(precedingthesentialforinflammationandthehostre-CXCsequence)andthosethatdonot(Fig.1).11Tsponsetoinfection.Theprocessiscontrol
5、ledThea-chemokinescontainingthesequenceareche-bychemokines,whicharechemotacticcytokines.motacticforneutrophils,whereasthosenotcontain-Thisreviewintroducestheburgeoningfamilyofcy-ingthesequenceactonlymphocytes.Forexample,tokines,withspecialemphasisonth
6、eirroleintheIP-10andMIG(monokineinducedbyinterferon-g)pathophysiologyofdiseaseandtheirpotentialastar-attractactivatedTcells,12andstromal-cell–derivedgetsfortherapy.factor1actsonrestinglymphocytes.13STRUCTUREANDFUNCTIONOFCHEMOKINESFigure1.Chemokinesand
7、TheirReceptors.Over40chemokineshavebeenidentifiedtodate,Thechemokinesarehomologous8-to-10-kdproteinsthataremostoftheminthepastfewyears.Therelationssubdividedintofamiliesonthebasisoftherelativepositionofamongchemokineswerenotinitiallyappreciated,thecys
8、teineresiduesinthematureprotein.Inthea-chemokines,thefirsttwocysteineresiduesareseparatedbyasingleaminowhichledtoanidiosyncraticnomenclatureconsist-acid(CXC),whereasintheb-chemokines,thefirsttwocysteineingofmanyacronyms.Wheninitiallyidentified
