A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-α
A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-α
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DOI：
10.1183/09031936.03.00303503
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发表时间：
2003-03-01
影响因子：
24.3
通讯作者：
Lindén, A
中科院分区：
文献类型：
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作者：
Laan, M;Prause, O;Lindén, A
T细胞细胞因子白细胞介素（IL）-17在体内选择性地在鼠气道中积聚嗜中性粒细胞，并且因此可能构成T淋巴细胞的活化和嗜中性粒细胞的积聚之间的联系。在这项研究中，作者评价了粒细胞巨噬细胞集落刺激因子（GM-CSF）在IL-17和肿瘤坏死因子（TNF）-α引起的气道中性粒细胞聚集中的作用。在体外，人（h）IL-17浓度依赖性地刺激人支气管上皮细胞（16 HBE）释放GM-CSF蛋白（酶联免疫吸附测定）。IL-17还在体外时间依赖性地刺激静脉内皮（人脐静脉内皮细胞）细胞中GM-CSF蛋白的释放。用IL-17加上促炎细胞因子TNF-α的共刺激增强了16 HBE细胞中GMCSF蛋白的释放。hIL-17还增强了16 HBE细胞中GM-CSF信使核糖核酸的表达（逆转录酶聚合酶链反应），其数量级与TNF-α相似。来自支气管上皮细胞的条件细胞培养基与hIL-17加TNF-α共刺激延长了体外人中性粒细胞的存活（台盼蓝排除），并且这种作用被抗GM-CSF抗体阻断。在体内，小鼠IL-17加TNF-α的局部共刺激引起小鼠气道支气管肺泡灌洗液中中性粒细胞累积的附加增强，并且这种作用被全身给予的抗GM-CSF抗体阻断。总之，粒细胞巨噬细胞集落刺激因子参与由白细胞介素-17和肿瘤坏死因子-α引起的气道中中性粒细胞的累积，可能通过对中性粒细胞的募集和存活的影响。
The T-cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airways in vivo and may thus constitute a link between activation of T-lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)-alpha.In vitro, human (h) IL-17 concentration-dependently stimulated the release of GMCSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cells in vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF-alpha potentiated the release of GMCSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF-alpha. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF-alpha prolonged survival (trypan blue exclusion) of human neutrophils in vitro and this effect was blocked by an anti-GM-CSF antibody. In vivo, local co-stimulation with mouse IL-17 plus TNF-alpha caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti-GM-CSF antibody given systemically.In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor-alpha, probably via effects on both recruitment and survival of neutrophils.