IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1.
IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1.
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DOI：
10.4049/jimmunol.148.4.1086
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发表时间：
1992-02
影响因子：
4.4
通讯作者：
R. Schleimer;S. A. Sterbinsky;James Kaiser;C. Bickel;David Klunk;K. Tomioka;W. Newman;F. Luscinskas;M. Gimbrone;B. McIntyre
中科院分区：
文献类型：
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作者：
R. Schleimer;S. A. Sterbinsky;James Kaiser;C. Bickel;David Klunk;K. Tomioka;W. Newman;F. Luscinskas;M. Gimbrone;B. McIntyre
本研究旨在探索白细胞粘附的潜在选择性机制，试图了解在过敏和其他炎症反应中嗜酸性粒细胞和嗜碱性粒细胞的优先募集是如何发生的。用IL-4 （30 - 1,000 U/ml）刺激人血管内皮细胞24小时，可诱导嗜酸性粒细胞（约为对照组的四倍）和嗜碱性粒细胞（约为对照组的两倍）粘附，但中性粒细胞不粘附（少于对照组的125%）。通过流式细胞术分析内皮细胞粘附分子的表达，发现IL-4处理诱导血管细胞粘附分子-1 （VCAM-1）的表达，但对内皮-白细胞粘附分子-1 （ELAM-1）或细胞间粘附分子-1 （ICAM-1）的表达无明显影响。il -4诱导VCAM-1表达的浓度-响应曲线与粘附的浓度-响应曲线相似。IL-4刺激内皮细胞3 h后表达了对嗜酸性粒细胞的粘附特性；在24小时的病程研究中，反应稳步增加。嗜酸性粒细胞和嗜碱性粒细胞粘附在涂有重组形式VCAM-1的板上。这种粘附被VCAM-1抗体阻断，但不能被ELAM-1抗体阻断。针对VCAM-1或vca -4的单抗可抑制（约75%）嗜酸性粒细胞和嗜碱性粒细胞与il -4刺激的内皮细胞的结合。由于vcam -4和VCAM-1已被证明在其他粘附系统中相互结合，这些结果表明，IL-4通过诱导内皮细胞表达VCAM-1来刺激嗜酸性细胞和嗜碱性细胞的粘附，VCAM-1与嗜酸性细胞和嗜碱性细胞vcam -4结合。中性粒细胞上缺乏VLA-4的表达和IL-4刺激中性粒细胞粘附的失败支持了这一结论。有人提出，在变应性疾病或实验性过敏原攻击后，体内IL-4的局部释放可能部分解释了在这些情况下观察到的嗜酸性粒细胞和嗜碱性粒细胞（相对于中性粒细胞）的富集。
The present studies were performed to explore potentially selective mechanisms of leukocyte adhesion in an attempt to understand how preferential recruitment of eosinophils and basophils might occur during allergic and other inflammatory reactions. Stimulation of human vascular endothelial cells for 24 h with IL-4 (30 to 1,000 U/ml) induced adhesion for eosinophils (up to approximately four-fold of control) and basophils (up to approximately twofold of control) but not neutrophils (less than 125% of control). Analysis of endothelial expression of adhesion molecules by flow cytometry revealed that IL-4 treatment induced vascular cell adhesion molecule-1 (VCAM-1) expression without significantly affecting the expression of other adhesion molecules, namely endothelial-leukocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1). The concentration-response curve for IL-4-induced VCAM-1 expression paralleled that for adhesion. Endothelial cells stimulated with IL-4 expressed adhesive properties for eosinophils by 3 h; the response increased steadily during a 24-h time course study. Eosinophils and basophils adhered to plates coated with a recombinant form of VCAM-1. This adhesion was blocked with antibodies to VCAM-1 but not ELAM-1. mAb directed against either VCAM-1 or VLA-4 inhibited (by approximately 75%) the binding of eosinophils and basophils to IL-4-stimulated endothelial cells. Because VLA-4 and VCAM-1 have been demonstrated to bind to each other in other adhesion systems, these results suggest that IL-4 stimulates eosinophil and basophil adhesion by inducing endothelial cell expression of VCAM-1 which binds to eosinophil and basophil VLA-4. The lack of expression of VLA-4 on neutrophils and the failure of IL-4 to stimulate neutrophil adherence support this conclusion. It is proposed that local release of IL-4 in vivo in allergic diseases or after experimental allergen challenge may partly explain the enrichment of eosinophils and basophils (vs neutrophils) observed in these situations.