THE RECEPTOR FOR INTERLEUKIN-3 IS SELECTIVELY INDUCED IN HUMAN ENDOTHELIAL-CELLS BY TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES INTERLEUKIN-8 SECRETION AND NEUTROPHIL TRANSMIGRATION
THE RECEPTOR FOR INTERLEUKIN-3 IS SELECTIVELY INDUCED IN HUMAN ENDOTHELIAL-CELLS BY TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES INTERLEUKIN-8 SECRETION AND NEUTROPHIL TRANSMIGRATION
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DOI：
10.1073/pnas.90.23.11137
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发表时间：
1993-12-01
影响因子：
11.1
通讯作者：
LOPEZ, AF
中科院分区：
文献类型：
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作者：
KORPELAINEN, EI;GAMBLE, JR;LOPEZ, AF
白细胞介素（IL）-3在体外刺激造血。然而，IL-3通常不存在于骨髓中，这对IL-3的体内作用提出了质疑。我们已经发现，人脐静脉内皮细胞（HUVEC）表达功能性高亲和力受体的IL-3刺激后与肿瘤坏死因子α（TNF-α），IL-1 β，或脂多糖，这种受体参与炎症现象。TNF-α引起IL-3受体α和β链mRNA的时间和剂量依赖性上调，最大效应发生在100单位/ml TNF-α刺激后16-36小时。通过单克隆抗体染色和HUVEC特异性结合I-125标记的IL-3的能力判断，mRNA的诱导与细胞表面的蛋白质表达相关。在TNF-α刺激的最佳条件下进行的Scatchard分析显示，每个细胞几乎等于1500个IL-3受体，其仅为高亲和力类别（K（d）= 500 pM）。与以前的报告相反，粒细胞-巨噬细胞集落刺激因子的受体不能被检测到。IL-3与TNF-α激活的HUVEC结合可增强IL-8的产生、E-选择素的表达和中性粒细胞的迁移。内皮细胞上功能性IL-3受体的选择性诱导表明，除了造血作用，IL-3可能在慢性炎症和过敏性疾病中起重要作用。
Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent upregulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind I-125-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed almost-equal-to 1500 IL-3 receptors per cell, which were of a high-affinity class (K(d) = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selectin expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation and in allergic diseases.