Schleimer R P, Sterbinsky S A, Kaiser J, Bickel C A, Klunk D A, Tomioka K, Newman W, Luscinskas F W, Gimbrone M A, McIntyre B W, Bochner B S
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
J Immunol. 1992 Feb 15;148(4):1086-92.
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.
进行本研究旨在探索白细胞黏附的潜在选择性机制，以试图理解在过敏及其他炎症反应期间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至1000 U/ml）刺激人血管内皮细胞24小时，可诱导嗜酸性粒细胞（高达对照的约四倍）和嗜碱性粒细胞（高达对照的约两倍）黏附，但不诱导中性粒细胞黏附（低于对照的125%）。通过流式细胞术分析黏附分子的内皮表达显示，IL-4处理诱导血管细胞黏附分子-1（VCAM-1）表达，而不显著影响其他黏附分子即内皮白细胞黏附分子-1（ELAM-1）或细胞间黏附分子-1（ICAM-1）的表达。IL-4诱导的VCAM-1表达的浓度-反应曲线与黏附的曲线平行。用IL-4刺激的内皮细胞在3小时时即表现出对嗜酸性粒细胞的黏附特性；在一项24小时的时间进程研究中，反应持续增加。嗜酸性粒细胞和嗜碱性粒细胞黏附于涂有重组形式VCAM-1的平板。这种黏附被抗VCAM-1抗体阻断，但不被抗ELAM-1抗体阻断。针对VCAM-1或VLA-4的单克隆抗体抑制（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。因为在其他黏附系统中已证明VLA-4和VCAM-1相互结合，这些结果表明IL-4通过诱导内皮细胞表达与嗜酸性粒细胞和嗜碱性粒细胞VLA-4结合的VCAM-1来刺激嗜酸性粒细胞和嗜碱性粒细胞黏附。中性粒细胞上缺乏VLA-4表达以及IL-不能刺激中性粒细胞黏附支持了这一结论。有人提出，在过敏性疾病中或实验性变应原激发后体内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。
