Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes
Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes
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DOI：
10.1046/j.1365-2567.2000.00061.x
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发表时间：
2000-08-01
期刊：
影响因子：
6.4
通讯作者：
Callard, RE
中科院分区：
文献类型：
--
作者：
Kotowicz, K;Dixon, GLJ;Callard, RE
血管内皮细胞上粘附分子的表达决定了炎症和免疫中白细胞的迁移和外渗模式。在这里，我们表明，共刺激与CD 40配体（CD 40 L）和白细胞介素（IL）-4（或IL-13）引起的粘附分子表达的人脐静脉内皮细胞（HUVEC）的独特模式。CD 40单独连接增强血管细胞粘附分子-1（VCAM-1）、细胞内粘附分子-1（ICAM-1）和E-选择素的表达，而IL-4和IL-13增加VCAM-1和P-选择素的表达，但不增加ICAM-1或E-选择素的表达。当IL-4和CD 40 L联合时，VCAM-1和P-选择素均增加，但ICAM-1和E-选择素均被抑制。IL-4和CD 40 L信号传导的联合作用不是反应动力学改变、内皮敏感性增强或CD 40或IL-4受体表达增加的结果。IL-4和CD 40 L联合刺激诱导的VCAM-1表达的增加比肿瘤坏死因子-α（TNF-α）更慢，更持久，并且仅发生在内皮细胞群的一个子集（75-80%）上，而TNF-α则为100%。IL-4和CD 40 L共刺激增加了T细胞和B细胞的粘附，高于单独使用任一信号获得的水平，但降低了中性粒细胞的粘附。此外，CD 40和IL-4协同增加HUVEC产生IL-6，但降低IL-8。这些结果表明，内皮细胞上的IL-4和CD 40之间的相互作用引起粘附分子表达和细胞因子产生的特定模式，这可能对淋巴细胞和中性粒细胞的迁移和炎症部位的功能具有重要意义。
The expression of adhesion molecules on vascular endothelial cells determines the pattern of migration and extravasation of leucocytes in inflammation and immunity. Here we show that costimulation with CD40 ligand (CD40L) and interleukin (IL)-4 (or IL-13) gives rise to a unique pattern of adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). CD40 ligation alone enhanced expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin whereas IL-4 and IL-13 increased expression of VCAM-1 and P-selectin but not ICAM-1 or E-selectin. When IL-4 and CD40L were combined there was an additional increase of both VCAM-1 and P-selectin, but ICAM-1 and E-selectin were both inhibited. The combined effects of IL-4 and CD40L signalling were not the result of altered response kinetics, enhanced sensitivity of the endothelium, or increased expression of CD40 or the IL-4 receptor. The rise in VCAM-1 expression induced by combined IL-4 and CD40L stimulation was slower and more sustained than with tumour necrosis factor-alpha (TNF-alpha) and occurred only on a subset (75-80%) of the endothelial cell population compared to 100% with TNF-alpha. Costimulation with IL-4 and CD40L increased adhesion of T cells and B cells above levels obtained with either signal alone, but decreased adhesion of neutrophils. Furthermore, CD40 and IL-4 synergistically increased IL-6 but decreased IL-8 production by HUVEC. These results show that interactions between IL-4 and CD40 on endothelial cells give rise to specific patterns of adhesion molecule expression and cytokine production that may have important implications for lymphocyte and neutrophil migration and function at sites of inflammation.