INTERLEUKIN-8 AS A MACROPHAGE-DERIVED MEDIATOR OF ANGIOGENESIS
INTERLEUKIN-8 AS A MACROPHAGE-DERIVED MEDIATOR OF ANGIOGENESIS
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DOI：
10.1126/science.1281554
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发表时间：
1992-12-11
期刊：
影响因子：
56.9
通讯作者：
STRIETER, RM
中科院分区：
文献类型：
--
作者：
KOCH, AE;POLVERINI, PJ;STRIETER, RM
由单核细胞-巨噬细胞产生的血管生成因子参与以持续性血管生成为特征的慢性炎症性疾病的发病机制。白细胞介素-8（IL-8）是一种对淋巴细胞和中性粒细胞具有趋化性的细胞因子，其也具有血管生成作用。人重组IL-8植入大鼠角膜后，可诱导人脐静脉内皮细胞的增殖和趋化性。炎症的人类风湿性滑膜组织巨噬细胞或脂多糖刺激的血液单核细胞的条件培养基中存在的血管生成活性同样被IL-8或肿瘤坏死因子-α的抗体阻断。IL-8反义寡核苷酸特异性阻断单核细胞诱导的血管生成活性的产生。这些数据表明巨噬细胞衍生的IL-8在血管生成依赖性疾病如类风湿性关节炎、肿瘤生长和伤口修复中的功能。
Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.