Expression And Their Significance Of CXCR3 And CCR5 (and Its Ligand) In PBMC And SFMC From Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common disease of causing cripple in the department of rheumatology. Its pathological changes include the hyper-proliferation and invasiveness of inflammatory cells in synovial tissue ,in which a ' inflammatory' phenomenon as activation and selective accumulation of Tlymphocytes in destructive synovitis is observed. But the mechanisms of this phenomenon are not fully understood ,which may be initiated through the chemokines and their ligands. Chemokines and it's receptor belongs to a rapidly expanding family of cytokines, the primary function of which is control of the correct positioning of cells in tissues and recruitment of leukocytes to the site of inflammation. Thl cells may play a central part in the pathophysiology of RA. CXCR3 or CCR5 and their ligands mediate activation of Thl lymphocytes and macrophages. Study of these very important inflammatory cytokines may greatly help our understanding of selective accumulation of Thl and other inflammatory cells in the progress of RA.The intracellular cytokine 1FN- y and IL-4 by, and the expression and distribution of CCR5 and CXCR3 on was studied, paired mononuclear cells in peripheral blood(PBMC) and synovial fluid(SFMC). We investigated the CCRS's ligand (MIP-1 and RANTES) also. Follow that, we study the regulation of CCR5 express on mononuclear cells inperipheral blood with IFN-R and Leflunomide ( one of effective addition to the therapeutic armamentarium for treating active RA).First, synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with active RA. The CD3+IFN-R+ or CD3+IL-4+ cells were verificated by three color flow cytometry. The result show that the selective pattern of intracellular cytokines in SFMC was drifted towords Thl subset.Second, the expressions of CCR5 and CXCR3 on T cells and monocyte/macrophage in PBMC and SFMC isolated from 16 patients with active RA were investigated. In the majority of the samples ,the percentage of CCR5+ and CXCR3+T cells, especially percentage of CCR5+ T cells , were much higher in SFMC (CCR5-78.87%, CXCR3-45.55%) than those of PBMC (CCR5-30.01%, CXCR3-40.88%) (P<0.05). The expressions of CCR5+ or CXCR3+ T cells in SFMC was consistent with expressionsof CD3+IFN-R(r >0.5, P<0.05). And the percentage of CCR5+ or CXCR3+ T cells in SFMC was correlated with the patient' of ESR and CRP(r>0.5, P<0.05).We also analysis the percent of MIP-1 P and RANTES in the SFMC and PBMC by flow cytometry as above. We found monocyte/macrophage and lymphocytes cells were both expressed MIP-1 & and RANTES, and the percent of them was higher in SFMC (CD14:29.16%,24.59%; L: 8.2%,12.3%) than in PBMC (CD14:10.14%,13.98; L:2.16%, 2.07%)(P<0.01).And third,in 10 samples of peripheral blood with active RA, the expressions of CCR5 were detected when IFN-r or Leflunomide in presence. The result identified elevated levels of CCR5 expression in presence of IFN- Y .While the expressions of CCR5 was restrained by Leflunomide.These data suggest that infiltrating T cells and macrophages in the lesion joints of RA can excrete MIP-1 and RANTES, which activate and attract the CCR5+ or CXCR3+ cells,and this cause the accumulation of CCR5+ orCXCR3+ Thl cells and macrophages. CCR5 may play a key role in the selective accumulation of lymphocytes in the lesion joints RA. The one of mechanisms Leflunomide treating active RA is gotten by CCR5.