Brown K A, Bedford P, Macey M, McCarthy D A, Leroy F, Vora A J, Stagg A J, Dumonde D C, Knight S C
Department of Immunology, UMDS, St Thomas' Hospital, London, UK.
Clin Exp Immunol. 1997 Mar;107(3):601-7. doi: 10.1046/j.1365-2249.1997.d01-951.x.
To investigate the binding properties of dendritic cells (DC) to vascular endothelium, a comparative analysis was undertaken of DC, monocytes and lymphocytes isolated from the blood of 25 healthy subjects using monolayers of human umbilical vein endothelial cells as the adherence substrate. More blood DC (mean 24% adherence) were adherent to endothelial monolayers than monocytes (mean 18%; P < 0.001) and lymphocytes (mean 12%; P < 0.001). When the monolayers were pretreated with tumour necrosis factor-alpha (TNF-alpha) all leucocyte populations exhibited an increased attachment, but there was still greater binding of DC (mean 37% adherence) in comparison with monocytes (mean 23%; P < 0.001) and lymphocytes (mean 18%; P < 0.001). Flow cytometric analysis revealed that in relation to monocytes and lymphocytes the DC had a higher surface expression of the adhesion molecules CD11a (P < 0.05), CD11c (P < 0.005) and CD54 (P < 0.005) but a lower prevalence of cells bearing CD49d (mean 38%; P < 0.05) and the homing receptor CD62L (mean 14%; P < 0.001). CD1a was present on 22% of DC and virtually absent from the surface of monocytes and lymphocytes. The intensity of expression of the beta1-integrins, CD49c, CD49d and CD49e was greater on DC than lymphocytes and monocytes (P < 0.05). Antibody blocking studies demonstrated that DC binding to untreated and TNF-alpha-treated endothelium was dependent upon the expression of CD11a, CD18 and CD49d, and the simultaneous application of anti-CD18 and anti-CD49d antibodies produced an approximate 70% inhibition of adhesion (P < 0.001). Thus, the expression of both beta1- and beta2-integrins contributes to the adhesive interaction between DC and endothelium.
为了研究树突状细胞(DC)与血管内皮的结合特性,以人脐静脉内皮细胞单层作为黏附底物,对从25名健康受试者血液中分离出的DC、单核细胞和淋巴细胞进行了对比分析。与单核细胞(平均黏附率18%;P<0.001)和淋巴细胞(平均黏附率12%;P<0.001)相比,更多的血液DC(平均黏附率24%)黏附于内皮细胞单层。当用肿瘤坏死因子-α(TNF-α)预处理单层时,所有白细胞群体的黏附均增加,但与单核细胞(平均黏附率23%;P<0.001)和淋巴细胞(平均黏附率18%;P<0.001)相比,DC的黏附仍然更高(平均黏附率37%)。流式细胞术分析显示,与单核细胞和淋巴细胞相比,DC表面黏附分子CD11a(P<0.05)、CD11c(P<0.005)和CD54(P<0.005)的表达更高,但携带CD49d的细胞比例较低(平均38%;P<0.05),归巢受体CD62L的比例也较低(平均14%;P<0.001)。22%的DC表面存在CD1a,而单核细胞和淋巴细胞表面几乎不存在。DC上β1整合素CD49c、CD49d和CD49e的表达强度高于淋巴细胞和单核细胞(P<0.05)。抗体阻断研究表明,DC与未处理和TNF-α处理的内皮的结合依赖于CD11a、CD18和CD49d的表达,同时应用抗CD18和抗CD49d抗体可产生约7折的黏附抑制(P<0.001)。因此,β1和β2整合素的表达均有助于DC与内皮之间的黏附相互作用。