Theinflammatoryresponseassociatedwithasthmaischaracterizedbytherecruitmentofeosinophilsfromthebronchialmicrocirculationinresponsetotheregulatedlocalproductionofchemoattractantmolecules.Althoughseveralchemicalmediatorsareactiveuponeosinophilsinvitro,acentralroleineosinophilaccumulationinvivoisemergingfortheC-Cchemokineeotaxin,whichwasfirstidentifiedinaguineapigmodelofallergicairwayinflammationusingproteinpurificationandmicrosequencing.Eotaxinisthedominanteosinophil-selectivechemoattractantinthismodel,actingtocausebothlocaleosinophilrecruitmenttothelung,andthereleaseofarapidlymobilizablepoolofbonemarroweosinophilsincooperationwithIL-5..Eotaxinandeotaxin-2arepotentstimulatorsofeosinophils,signalingexclusivelyviahighaffinitybindingtothereceptorCCR3.C-Cchemokines,includingMCP-3,MCP-4,andRANTES,alsostimulateeosinophilsviaCCR3,althoughtheyshowlessleukocyteselectivityastheyadditionallysignalviaotherchemokinereceptorsexpressedonarangeofleukocytes,includinglymphocytesandmonocytes.CCR3isexpressedinhighnumbersoneosinophilsandisthoughttobethemajoreosinophilchemokinereceptor.BlockadeofCCR3invivoinhibitseosinophilrecruitmentinresponsetoeotaxininboththeguineapigandmouse.Morerecently,CCR3expressionhasbeendemonstratedonbasophilsandTh2-typeTcells,suggestingpossIBLerolesforCCR3inthegenesisandmaintenanceofallergicinflammation.CCR3isthereforeamajortargetforanti-inflammatorydrugdevelopment

Contributor:MichaelShih,PhD

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