BRONCHIAL EPITHELIAL CELL-DERIVED CYTOKINES (G-CSF AND GM-CSF) PROMOTE THE SURVIVAL OF PERIPHERAL-BLOOD NEUTROPHILS INVITRO
BRONCHIAL EPITHELIAL CELL-DERIVED CYTOKINES (G-CSF AND GM-CSF) PROMOTE THE SURVIVAL OF PERIPHERAL-BLOOD NEUTROPHILS INVITRO
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DOI：
10.1165/ajrcmb/7.5.507
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发表时间：
1992-11-01
影响因子：
6.4
通讯作者：
JORDANA, M
中科院分区：
文献类型：
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作者：
COX, G;GAULDIE, J;JORDANA, M
呼吸道中的中性粒细胞积聚发生在多种炎症性疾病中，特别是与吸烟相关的炎症性疾病。我们检查了支气管上皮细胞是否可以通过产生增加中性粒细胞存活的因子来促进这种积累。使用人支气管上皮细胞（HBEC）的纯原代培养物产生条件培养基（CM），并检查该CM对体外中性粒细胞存活的影响。当中性粒细胞在对照培养基中培养时，72 小时时的存活率为 8.7 +/- 1.7%。相比之下，CM 中的中性粒细胞培养导致存活率呈剂量依赖性增加：1%、10% 和 50% CM 中分别增加 22.6 +/- 5.5、43.6 +/- 4.2 和 64 +/- 3.8%（平均值 +/- SEM；P < 0.05）。中性粒细胞 DNA 检查证明，这种生存期的延长与细胞凋亡的抑制有关。 CM 中发现的对中性粒细胞生物学具有已知作用的细胞因子包括粒细胞集落刺激因子 (G-CSF)、粒细胞/巨噬细胞集落刺激因子 (GM-CSF) 和白细胞介素 8。通过使用特异性中和抗体，G-CSF 和 GM-CSF 被确定可促进中性粒细胞存活。在重组人 (rh) G-CSF 或单独的 rhGM-CSF 存在下，中性粒细胞的存活时间以剂量依赖性方式延长。与嗜酸性粒细胞对 HBEC-CM 的反应相反，类固醇治疗并不能阻止 HBEC-CM 诱导的中性粒细胞存活率的增加。总之，我们表明支气管上皮细胞通过释放G-CSF和GM-CSE显着增加体外人中性粒细胞的存活。这样，HBEC细胞可能有助于体内慢性炎症期间中性粒细胞的积累。
Neutrophil accumulation in the respiratory tract occurs in a variety of inflammatory disorders, particularly those associated with cigarette smoking. We examined whether bronchial epithelial cells could contribute to this accumulation through the production of factors that increased the survival of neutrophils. Pure primary cultures of human bronchial epithelial cells (HBEC) were used to generate conditioned medium (CM), and the effect of this CM on the survival of neutrophils in vitro was examined. When neutrophils were cultured in control medium, survival was 8.7 +/- 1.7% at 72 h. In contrast, culture of neutrophils in CM resulted in a dose-dependent increase in survival: 22.6 +/- 5.5, 43.6 +/- 4.2, and 64 +/- 3.8% in 1, 10, and 50% CM respectively (mean +/- SEM; P < 0.05). As evidenced by the examination of neutrophil DNA, this prolongation of survival was associated with suppression of apoptosis. Cytokines with known actions on neutrophil biology identified in the CM included granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM-CSF were identified as promoting neutrophil survival. Neutrophil survival was prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF alone in a dose-dependent fashion. In contrast to the response of eosinophils to HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly increase die survival of human neutrophils in vitro via the release of G-CSF and GM-CSE In this way, HBEC cells might contribute to the accumulation of neutrophils during chronic inflammation in vivo.