5′‐AMP impacts lymphocyte recirculation through activation of A2B receptors

[摘要] Naturalhibernationconsistsoftorpidphaseswithmetabolicsuppressionalternatingwitheuthermicperiods.Inductionoftorporholdssubstantialpromiseinvariousmedicalconditions,includingtrauma,majorsurgery,andtransplantation.Torporinmicecanbeinducedpharmacologicallyby5′‐AMP.Previously,weshowedthatduringnaturaltorpor,thereductioninbodytemperatureresultsinlymphopeniaviaareductioninplasmaS1P.Here,weshowthatduringtorporinducedby5′‐AMP,thereisasimilarreductioninthenumberofcirculatinglymphocytesthatisaresultoftheirretentioninsecondarylymphoidorgans.ThislymphopeniacouldbemimickedbyengagementofA2BRsbyaselectiveA2BRagonist(LUF6210)intheabsenceofchangesintemperatureandpreventedbyA2BRantagonistsduring5′‐AMP‐inducedtorpor.Inaddition,forcedcoolingofmiceledtoperipheralbloodlymphopenia,independentofA2BRsignaling.Theinductionoftorporusing5′‐AMPimpactedthemigrationoflymphocyteswithinandbetweensecondarylymphoidorgans.Duringtorpor,thehomingintoLNswasimpaired,andtwo‐photonintravitalmicroscopyrevealedthatcellmotilitywasdecreasedsignificantlyandrapidlyupon5′‐AMPadministration.Furthermore,theS1Pplasmaconcentrationwasreducedby5′‐AMPbutnotbyLUF6210.S1Pplasmalevelsrestoreduponarousal.Likely,thereducedmigrationinLNscombinedwiththereducedS1Pplasmalevelsubstantiallyreduceslymphocyteegressafterinjectionof5′‐AMP.Inconclusion,5′‐AMPinducesastateofpharmacologicaltorporinmice,duringwhich,lymphopeniaisgovernedprimarilybybodytemperature‐independentsuppressionoflymphocyteegressfromLNs...

[学科分类] 生理学

[关键词] hibernation;anesthesiology;inflammation;suspended animation;metabolism