Thornhill M H, Kyan-Aung U, Haskard D O
Rheumatology Unit Medical School, Guy's Hospital, London, UK.
J Immunol. 1990 Apr 15;144(8):3060-5.
The adhesion of leukocytes to vascular endothelium is the first step in their passage from the blood into inflammatory tissues. By modulating endothelial cell (EC) adhesiveness for leukocytes, cytokines may regulate leukocyte accumulation and hence the nature and progression of inflammatory responses. We have found that the T cell cytokine IL-4 increases the adhesion of T cells, but not neutrophils, to human umbilical vein EC monolayers. The increase in T cell adhesion induced by IL-4 was dose dependent (ED50 = 5 U/ml) and peaked around 33 U/ml. No increase in adhesion of neutrophils was observed at concentrations of IL-4 up to 1000 U/ml. The kinetic of the increase in T cell adhesion exhibited a steady rise peaking between 18 and 24 h before returning to basal levels by 72 h. The IL-4 specificity of the effect was confirmed by the ability of neutralizing anti-IL-4, but not anti-TNF, antibodies to abolish the effect. The increase in T cell-EC adhesion was due to an effect of IL-4 on EC inasmuch as preincubation of the T cells with IL-4 did not increase T cell binding. Furthermore, preincubation of A549 epithelial cell line monolayers with IL-4 caused no increase in T cell binding whereas A549 cells and EC showed a similarly enhanced adhesiveness for T cells after preincubation with IL-1, TNF, or IFN-gamma. EC treated with IL-4 retained their increased adhesiveness for T cells after light fixation, suggesting that IL-4 up-regulates binding by increasing the expression or accessibility of EC surface receptors for lymphocytes. Although antibodies to intercellular adhesion molecule-1 (CD54) and the beta-chain (CD18) of lymphocyte function-associated Ag-1 (CD11a/CD18) partially inhibited T cell adhesion to unstimulated EC, they did not affect the increase in adhesion due to IL-4 stimulation, indicating that the increased binding resulted from the generation of an alternative binding receptor(s) on the EC membrane. These findings suggest that IL-4 may play a role in the selective recruitment of T cells into sites of immune-mediated chronic inflammation.
白细胞与血管内皮的黏附是其从血液进入炎症组织的第一步。通过调节内皮细胞（EC）对白细胞的黏附性，细胞因子可能调控白细胞的聚集，进而影响炎症反应的性质和进程。我们发现，T细胞细胞因子IL-4可增加T细胞与人脐静脉EC单层的黏附，但不增加中性粒细胞的黏附。IL-4诱导的T细胞黏附增加呈剂量依赖性（ED50 = 5 U/ml），在约33 U/ml时达到峰值。在高达1000 U/ml的IL-4浓度下，未观察到中性粒细胞黏附增加。T细胞黏附增加的动力学表现为稳步上升，在18至24小时达到峰值，然后在72小时恢复到基础水平。通过中和抗IL-4而非抗TNF抗体消除该效应，证实了该效应的IL-4特异性。T细胞与EC黏附的增加是由于IL-4对EC的作用，因为用IL-4预孵育T细胞不会增加T细胞的结合。此外，用IL-4预孵育A549上皮细胞系单层不会增加T细胞结合，而在用IL-1、TNF或IFN-γ预孵育后，A549细胞和EC对T细胞的黏附性同样增强。用IL-4处理的EC在轻度固定后仍保持对T细胞增加的黏附性，表明IL-4通过增加EC表面淋巴细胞受体的表达或可及性来上调结合。尽管抗细胞间黏附分子-1（CD54）和淋巴细胞功能相关抗原-1（CD11a/CD18）的β链（CD18）抗体部分抑制T细胞对未刺激EC的黏附，但它们不影响IL-4刺激导致的黏附增加，表明增加的结合是由于在EC膜上产生了替代结合受体。这些发现表明，IL-4可能在将T细胞选择性募集到免疫介导的慢性炎症部位中发挥作用。
