Receptor cleavage and P‐selectin‐dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: glycoprotein ligand 1;    matrix metalloproteinase;    mesentery;    extracellular receptor density;    leukocyte rolling;    MMP inhibitor;   

DOI  :  10.1189/jlb.0112010

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheSHR,ageneticmodelforhypertensionandthemetabolicsyndrome,hasattenuatedleukocyteadhesiontothepostcapillaryendotheliumbyanunknownmechanism.BasedonrecentevidenceofelevatedlevelsofMMPsinplasmaandonmicrovascularendotheliumoftheSHRwithcleavageofseveralreceptortypes,wehypothesizethatthereducedleukocyte‐endothelialinteractionisaresultofenhancedproteolyticcleavageofP‐selectinonthepostcapillaryendotheliumandPSGL‐1onleukocytes.TheattenuatedrollinginteractionsofSHRleukocyteswiththeendotheliumwererestoredbychronictreatmentwithabroad‐spectrumMMPinhibitor(CGS)for24weeks.TheSHRMMPlevels,inplasmaandmesentery,aswellasthesystolicbloodpressure,decreasedsignificantlywithtreatment.IntheSHRmesentery,labelingofP‐selectininthepostcapillaryvenulesbyimmunohistochemistrydemonstrated,onaverage,a31%lowerextracellularP‐selectindensitycomparedwiththenormotensiveWKY.AsignificantlylowerextracellularPSGL‐1densityonthemembranesofSHRneutrophilscomparedwiththeWKYalsosupportedourhypothesis.InvivostimulationofthemesentericpostcapillaryvenuleswithhistaminedemonstratedthattheSHRhadanattenuatedresponse,asmeasuredbyleukocyterollingvelocityontheendothelium.ThereducedP‐selectinandPSGL‐1density,onSHRpostcapillaryendotheliumandonSHRleukocytes,respectively,wasrestoredsignificantlybychronicMMPinhibition.TheimpairedabilityofSHRleukocytestoreducerollingvelocityuponinflammatorystimulationledtofewerfirmlyadheredleukocytestotheendotheliumasacontributortoimmunesuppression...

【 授权许可】

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