König A, Krenn V, Toksoy A, Gerhard N, Gillitzer R
Department of Orthopaedics, University of Würzburg, Germany.
Virchows Arch. 2000 May;436(5):449-58. doi: 10.1007/s004280050472.
To investigate lymphocyte and monocyte recruitment-specific chemokine expression in synovial tissues from patients with rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA), synovial membranes and cytocentrifuge preparations of 7 RA, 8 PA and 10 OA patients were examined by in situ hybridisation with antisense probes of Mig, GRO alpha and RANTES and by immunohistochemistry. Patients' local disease activity (swelling and tenderness) in order to was graded and histological evaluation was performed compare these data with their chemokine expression profiles. Mig and RANTES hybridisation signals were detected in the synovial lining layer and in cellular infiltrates, whereas GRO alpha expression was localised exclusively in the lining layer of PA and RA. Cytological analysis revealed Mig and GRO alpha mRNA mainly in monocytic cells expressing KIM6, while RANTES mRNA was demonstrated predominantly in lymphocytic cells expressing CD3. In OA synovial membranes, significantly fewer hybridisation signals were present than in RA and PA synovial membranes. Patients with PA and RA had mild to severe local disease activity, whereas OA patients showed only mild disease activity. Histologically, PA and RA inflammatory scores ranged from 1 to 5, while OA synovium was consistently graded 1. Therefore, we conclude that the differential expression of Mig, GRO alpha and RANTES in resident and in inflammatory cells has an important role in regulating leucocyte traffic in inflammatory arthropathies. The diverse leucocyte specificity of Mig, GRO alpha and RANTES may thus regulate the recruitment of different leucocyte populations, as detected in PA and RA. Therefore, the pattern of cellular infiltration in human synovitis and the corresponding clinical signs of inflammation basically reflect the localisation and expression intensity of chemokines, which may be an important target for future disease modulation.
为研究类风湿性关节炎(RA)、银屑病关节炎(PA)和骨关节炎(OA)患者滑膜组织中淋巴细胞和单核细胞募集特异性趋化因子的表达情况,采用Mig、GROα和RANTES反义探针原位杂交及免疫组化方法,检测了7例RA、8例PA和10例OA患者的滑膜及细胞离心涂片。对患者的局部疾病活动度(肿胀和压痛)进行分级,并进行组织学评估,以便将这些数据与其趋化因子表达谱进行比较。在滑膜衬里层和细胞浸润中检测到Mig和RANTES杂交信号,而GROα表达仅局限于PA和RA的衬里层。细胞学分析显示,Mig和GROα mRNA主要存在于表达KIM6的单核细胞中,而RANTES mRNA主要在表达CD3的淋巴细胞中检测到。在OA滑膜中,杂交信号明显少于RA和PA滑膜。PA和RA患者有轻度至重度的局部疾病活动度,而OA患者仅表现为轻度疾病活动度。组织学上,PA和RA的炎症评分为1至5分,而OA滑膜始终评分为1分。因此,我们得出结论,Mig、GROα和RANTES在驻留细胞和炎症细胞中的差异表达在调节炎症性关节病中白细胞的迁移方面具有重要作用。Mig、GROα和RANTES不同的白细胞特异性可能因此调节不同白细胞群体的募集,如在PA和RA中检测到的那样。因此,人类滑膜炎中的细胞浸润模式和相应的炎症临床体征基本上反映了趋化因子的定位和表达强度,这可能是未来疾病调控的一个重要靶点。