Research On The Association Between The Expression Of CX3CR1 On Peripheral Blood Mononuclear Cells And Coronary Artherosclerosis

Artherosclerosis is a chronic infammation process. ArteryEndotheliocyte is the beginning spot of inflammation and immuneattack,many kinds of inflammatory medium participate the formationof AS.The investigation indicate that the chemotatic factor Fractalkinehas the important significance during the process of the form ofAS.Fractalkine is a different chemotatic factor,it exists in the plaqueof AS by means of membrane combining form and dissolvable format the same time.Now it has been confirmed that FKN of membranecombining form has the effect as adhesion molecule.and thedissolvable form has chemotaxis to monocyte,T-cell,and naturalkiller cell. chemotatic factor FKN expresses on macrophagocytesubunit,and we consider that it is possibly the significant marker ofTH1 and TH2 immune reaction during artherosclerosis.Themechanism possibly is that FKN combined with the GPCR CX3CR1that transmembrane seven times and initiate the G protein link-coup-led signal transduction .It makes various kinds of cell that expressthis receptor especially leukomonocyte,mononuclear macrophagegenerates directionality migrated signal,and can efficiently spanningblood vessel and migrate to the special spot at outside of bloodvessel,and participate in the formation of atherosclerotic.Yonedo andso on have discover that inflammatory cytokine IL-1β,TNF-αandLPS predominantly up-regulate that endotheliocyte express FKN isthrough the mechanism of KB dependent,and FKN can combinedwith latest distinct natural killer cell(NK),and enhance the lethalityof NK cell by means of dose-dependent, accordingly induceendotheliocyte damage.This effect can be rivalry by dissoluble FKNantibody or anti-CX3CR1.These hint that FKN participate in NK cellmediated endothelium damage.Chemotatic factor FKN is expressed by inflamedendotheliocyte,it combined with receptor CX3CR1 and induceleucocyte adhere and migrate,we consider that this is theindependent risk factor of coronary atherosclerosis. The adhesionand aggregation of leucocyte on endotheliocyte need adhesionmolecule and chemotatic factor.Chemotatic factor FKN hastransmembrane domain,so it can fleetly mediate resting mononuclearmacrophage and CD-8+T cell stimulant by IL-2 and NK cellchemotatic. The construction of CX3C in the construction of FKNplay a part in tendency function,it combined with N extrem.ofreceptor CX3CR1, mucoprotein-like construction play a part intransmit molecular action.FKN also can mediate intercellularsticky,and it needn't G-protein's activation and up-regulation ofintegrin,and the sticky character of circulating NK cells that mediateby FKN can induce endotheliocyte damage. Membrane type FKNpromote leukocyte adhesion needn't selectin ,conglutinin and otherintercellular adhesion molecule participate. Otherwise,FKN canstrengthen macrophage-like TRP-1 cell and monocaryotic cell stickwith ICAM-1.These phenomenon indicates that any factor that effectthe expression level of CX3CR1 can effect leucocytic flow andinduce reciprocal disease such as CAD.Accordingly through detect the expression level of CX3CR1 inperipheral blood monouclear cells possibly conduce to earlydiagnosis Atherosclerotic disease such as CAD and AMI andinvariably appraisal the senerity and prognosis,and use neutralityantibody of CX3CR1 to relieve inflammatory reaction,or throughgene knock-out/ replace means and so on can possibly prevent thegenerate and development of atherosclerotic process, thereby canprofit the clinical prevention and cure of AS,AMI and othercardiovascular disease.Experiment objective:1) investigate the influence ofFKN/CX3CR1 to atherogenesis.2) investigate the associativitybetween the expression level of CX3CR1 on peripheral bloodmononuclear cells and coronary artherosclerosis.3) investigate thedifference of the expression level of CX3CR1 on peripheral bloodmononuclear cells in patient of AMI,UAP,SAP.empirical method: Extract peripheral blood mononuclear cellsfrom the patient of AMI,UAP,SAP group and normal group,take100ul cell suspension,add 20ul rat-anti-human cx3cr1/FITC in sampletube;incubation 20 min at 4℃;cleaning by PBS two times, downsuspension cells by 200ul PBS,keep the ambient temperature at 4℃and get into machine now;use FACSort flow cytometry flowcytometer(American Becton Dickinson company) according to thediffrence of antibody labeling on cell surface to run cell sorting,counting 1×l04 cells,use Cell Quest software analyse data.Use meanfluorescence intensity(MFI)represent the expression level of cellsand record result.experimental result:1) MFI of CX3CR1 on peripheral bloodmononuclear cells in patient of AMI,UAP,SAP group is obviouslyhigher than normal group.2)MFI of CX3CR1 on peripheral bloodmononuclear cells in patient of AMI,UAP,SAP group presentdecremental tendency.Conclusion:1) MFI of CX3CR1 on peripheral bloodmononuclear cells in patient of AMI,UAP,SAP group is obviouslyhigher than normal group. Macroscopic testify the proceeding ofartherosclerosis is by means of up-regulation the expression ofCX3CR1,FKN/CX3CR1 have the effect iveness of promotingatherogenesis.2) MFI of CX3CR1 on peripheral blood mononuclearcells in patient of AMI,UAP,SAP group present decrementaltendency, the expression of CX3CR1 on peripheral bloodmononuclear cells in patient of AMI obviously advance,it testify thatthe expression level of CX3CR1 on peripheral blood mononuclearcells positive correlate with the severity degree of pathogeneticcondition.This will conduce to early diagnosis Atheroscleroticdisease such as CAD,AMI and invariably appraisal the senerity andprognosis,and use neutrality antibody of CX3CR1 to relieveinflammatory reaction,or through gene knock-out/ replace means andso on can possibly prevent the generate and development ofatherosclerotic process, thereby can profit the clinical prevention andcure of AS,AMI and other cardiovascular disease.