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类风湿关节炎中的血液单核细胞活化:单核细胞黏附性增加、整合素表达增加及细胞因子释放。

Blood monocyte activation in rheumatoid arthritis: increased monocyte adhesiveness, integrin expression, and cytokine release.

作者信息

Lioté F, Boval-Boizard B, Weill D, Kuntz D, Wautier J L

机构信息

Clinique de Rhumatologie, Assistance Publique-Hôpitaux de Paris, France.

出版信息

Clin Exp Immunol. 1996 Oct;106(1):13-9. doi: 10.1046/j.1365-2249.1996.d01-820.x.

DOI:10.1046/j.1365-2249.1996.d01-820.x
PMID:8870692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2200557/
Abstract

Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA-4), and CD49e (VLA-5) on monocytes from patients with RA and from normal (N) subjects. IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin-coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL-1 beta. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80-466) units; normal Mo = 95 (range 24-164) units; P < 0.003). Production of extracellular IL-1 beta and IL-6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL-1 beta: RA = 2.65 +/- 0.91 ng/ml versus N = 1.35 +/- 0.85 pg/ml, P < 0.05; IL-6: RA = 4.83 +/- 0.90 ng/ml versus N = 2.40 +/- 0.95 ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P < 0.01; fibronectin, P < 0.01; and gelatin-coated normal or RA plasma, P < 0.01) as well as to unstimulated (P < 0.01) and IL-1 beta-stimulated endothelial cells (IL-1 beta for 4 h, P < 0.05; IL-1 beta for 24h, P < 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.

摘要

滑膜被单核细胞(即淋巴细胞和单核细胞)浸润是类风湿性关节炎(RA)的主要特征之一,被认为与该疾病的发展有关。在这项针对31例连续RA患者的研究中,我们调查了外周血单核细胞是否表现出与细胞迁移相关的细胞活化标志物。使用带有各自特异性抗体的流式细胞术,我们研究了RA患者和正常(N)受试者单核细胞上整合素CD11a、CD11b、CD11c、CD49d(VLA - 4)和CD49e(VLA - 5)的表达。通过免疫测定法测量培养的单核细胞产生的白细胞介素 - 1β(IL - 1β)、白细胞介素 - 6(IL - 6)和肿瘤坏死因子 - α(TNF - α)。在基础条件下或经IL - 1β刺激后,研究了单核细胞在各种表面(塑料、人纤连蛋白、明胶包被的血浆、内皮下基质)以及培养的内皮细胞上的黏附性。来自RA患者的CD14⁺单核细胞(Mo)中表达CD11b分子的数量增加(RA Mo = 90.3%,N Mo = 83.4%,P < 0.005)。RA患者中CD14⁺单核细胞上CD11b的表达显著增加(中位荧光强度(FI):RA Mo = 145(范围80 - 466)单位;正常Mo = 95(范围24 - 164)单位;P < 0.003)。与正常受试者的单核细胞相比,RA单核细胞产生细胞外IL - 1β和IL - 6的能力显著增强(IL - 1β:RA = 2.65 ± 0.91 ng/ml,而N = 1.35 ± 0.85 pg/ml,P < 0.05;IL - 6:RA = 4.83 ± 0.90 ng/ml,而N = 2.40 ± 0.95 ng/ml,P < 0.05)。与正常单核细胞相比,RA单核细胞对所研究的各种表面(塑料,P < 0.01;纤连蛋白,P < 0.01;明胶包被的正常或RA血浆,P < 0.01)以及未刺激的(P < 0.01)和IL - 1β刺激的内皮细胞(IL - 1β刺激4小时,P < 0.05;IL - 1β刺激24小时,P < 0.05)表现出更强的黏附性。在我们的研究中,RA患者的血液单核细胞表现出与细胞黏附相关的活化特征。