Katschke K J, Rottman J B, Ruth J H, Qin S, Wu L, LaRosa G, Ponath P, Park C C, Pope R M, Koch A E
Northwestern University Medical School, Chicago, Illinois 60611, USA.
Arthritis Rheum. 2001 May;44(5):1022-32. doi: 10.1002/1529-0131(200105)44:5<1022::AID-ANR181>3.0.CO;2-N.
Since it is likely that monocytes utilize chemokines to migrate to the rheumatoid arthritis (RA) joint, we investigated the expression of C-C chemokine receptors (CCR) 1-6 and C-X-C receptor 3 (CXCR3) in the peripheral blood (PB), synovial fluid (SF), and synovial tissue of patients with RA as well as in the PB of normal subjects.
We compared chemokine receptor expression on CD14+ monocytes from normal PB, RA PB, and RA SF using 2-color flow cytometry. Correlations with patient clinical data were determined. Chemokine and receptor expression were investigated in RA synovial tissue by immunohistochemistry and 2-color immunofluorescence to identify CD68+ macrophages.
Most normal PB monocytes expressed CCR1 (87%) and CCR2 (84%), but not CCRs 3, 4, 5, or 6 or CXCR3. RA PB monocytes expressed CCR1 (56%) and CCR2 (76%), with significantly more expressing CCR3 (18%), CCR4 (38%), and CCR5 (17%) compared with normal PB monocytes. Significantly fewer SF monocytes from RA patients expressed CCR1 (17%), CCR2 (24%), and CCR4 (6%) while significantly more expressed CCR3 (35%) and CCR5 (47%) compared with RA and normal PB monocytes; CCR6 and CXCR3 were rarely detected. Clinically, the erythrocyte sedimentation rate was inversely correlated with the expression of CCR1 and CCR4 by RA PB, and CCR5 expression by RA SF was correlated with the SF white blood cell count. CCR1-, CCR2-, and CCR5-immunoreactive cells were found in RA synovial tissue and colocalized with CD68+ macrophages. RA synovial tissue RANTES (regulated upon activation, normally T cell expressed and secreted chemokine)- and monocyte chemoattractant protein 1-immunoreactive cells colocalized with CCR1 and CCR2, respectively, on serial sections. Macrophage inflammatory protein 1alpha (MIP-1alpha) was principally restricted to vascular endothelium, and MIP-1beta+ macrophages were found throughout the sections.
Monocytes mainly express CCR1 and CCR2 in normal and RA PB, CCR3 and CCR5 in RA PB and RA SF, and CCR4 in RA PB. The differential expression of chemokine receptors suggests that certain receptors aid in monocyte recruitment from the circulation while others are important in monocyte retention in the joint.
由于单核细胞可能利用趋化因子迁移至类风湿关节炎（RA）关节，我们研究了RA患者外周血（PB）、滑液（SF）和滑膜组织以及正常受试者PB中C-C趋化因子受体（CCR）1 - 6和C-X-C受体3（CXCR3）的表达情况。
我们使用双色流式细胞术比较了正常PB、RA PB和RA SF中CD14⁺单核细胞上趋化因子受体的表达情况。确定了其与患者临床数据的相关性。通过免疫组织化学和双色免疫荧光法研究RA滑膜组织中的趋化因子和受体表达，以鉴定CD68⁺巨噬细胞。
大多数正常PB单核细胞表达CCR1（87%）和CCR2（84%），但不表达CCR3、4、5、6或CXCR3。RA PB单核细胞表达CCR1（56%）和CCR2（76%），与正常PB单核细胞相比，表达CCR3（18%）、CCR4（38%）和CCR5（17%）的细胞明显更多。与RA和正常PB单核细胞相比，RA患者SF单核细胞中表达CCR1（17%）、CCR2（24%）和CCR4（6%）的细胞明显减少，而表达CCR3（35%）和CCR5（47%）的细胞明显增多；CCR6和CXCR3很少被检测到。临床上，红细胞沉降率与RA PB中CCR1和CCR4的表达呈负相关，RA SF中CCR5的表达与SF白细胞计数相关。在RA滑膜组织中发现了CCR1、CCR2和CCR5免疫反应性细胞，并与CD68⁺巨噬细胞共定位。在连续切片上，RA滑膜组织中受激活调节正常T细胞表达和分泌的趋化因子（RANTES）和单核细胞趋化蛋白1免疫反应性细胞分别与CCR1和CCR2共定位。巨噬细胞炎性蛋白1α（MIP-1α）主要局限于血管内皮，在整个切片中均发现了MIP-1β⁺巨噬细胞。
单核细胞在正常和RA PB中主要表达CCR1和CCR2，在RA PB和RA SF中表达CCR3和CCR5，在RA PB中表达CCR4。趋化因子受体的差异表达表明，某些受体有助于单核细胞从循环中募集，而其他受体在单核细胞在关节中的滞留中起重要作用。
