FcγRI mediates serum amyloid P inhibition of fibrocyte differentiation

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

关键词: monocyte;    SAP;    CD64;    CD32;    pentraxin;   

DOI  :  10.1189/jlb.0112033

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Fibroticdiseases,suchascardiacandpulmonaryfibrosis,haveapoorprognosiswithnoFDAapprovedtherapies.Monocyte‐derived,fibroblast‐likecells,calledfibrocytes,participateintheformationoffibroticlesions.TheconservedpentraxinproteinSAPinhibitsfibrocytedifferentiationincellculture,andinjectionsofSAPsignificantlyreducefibrosisinseveralanimalmodels.SAPbindstothereceptorsfortheFcportionofIgG(FcγR)andhasbeencrystallizedboundtoFcγRIIa(CD32a).TheinvivoactivityofSAPappearstobedependentontheFcRγ.WefindthatmutagenesisoftheresiduescriticalforSAPbindingtoFcγRIIaonlymoderatelydecreasestheabilityofSAPtoinhibitfibrocytedifferentiation.Inmurinecells,deletionofFcRγorFcγRI(CD64)significantlyreducedsensitivitytoSAP.DeletionofthecombinationofFcγRIIb,FcγRIIIa,andFcγRIVdidnotsignificantlyaffectsensitivitytoSAP,whereasdeletionofjusttheinhibitoryreceptorFcγRIIb(CD32b)increasedsensitivitytoSAP.Inhumancells,siRNA‐mediatedreductionofFcRγorFcγRIlevelssignificantlydecreasedsensitivitytoSAP,whereasreductionofFcγRIIblevelsincreasedsensitivitytoSAP.TheseobservationssuggestthatSAP,atleastinpart,usesFcγRIandFcRγtoinhibitfibrocytedifferentiation...

【 授权许可】

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