抗哮喘药物对A549细胞吞噬清除凋亡嗜酸性粒细胞作用的影响
2009/08/11
背景：对凋亡的嗜酸性粒细胞的吞噬清除在哮喘炎症治疗中具有重要作用。据我们了解，有关支气管上皮细胞对凋亡的嗜酸性粒细胞的吞噬清除作用研究较少。
目的：本研究评价了地塞米松、氨茶碱及特布他林对A549细胞吞噬清除凋亡嗜酸性粒细胞作用的影响。
方法：对来自5个正常志愿者的外周血采用CD15、CD16依赖的免疫磁珠对嗜酸性粒细胞进行筛选。在显微镜下观察、评价A549对凋亡的嗜酸性粒细胞的吞噬能力。用RIA检测A549细胞培养液中的IL-6和IL-8浓度。
结果：地塞米松能增加A549细胞的吞噬能力，抑制LPS刺激后A549细胞的IL-6和IL-8分泌量。有意思的是，氨茶碱和特布他林不仅能以时间或剂量依赖的方式下调A549细胞对凋亡嗜酸性粒细胞的吞噬清除作用，也能降低A549细胞在受LPS刺激后的IL-6和IL-8分泌量。
结论：本研究显示，抗哮喘药物（地塞米松、氨茶碱及特布他林）可以通过降低A549细胞在LPS刺激后的IL-6和IL-8分泌量来发挥其抗炎作用。另外，这些药物对A549细胞吞噬清除凋亡的嗜酸性粒细胞的作用并不一致，如地塞米松能促进吞噬清除，氨茶碱和特布他林则抑制对凋亡嗜酸性粒细胞的清除。上述结果揭示了地塞米松、氨茶碱及特布他林治疗哮喘的新的作用机制。
（苏楠 审校）
Wang J, et al. Respir Med. 2009 Jun 12. [Epub ahead of print]
The effects of anti-asthma drugs on the phagocytic clearance of apoptotic eosinophils by A549 cells.
Wang J, Wang C, Li X, Kong L, Gao K, Liu RY.
Department of Pulmonary, Anhui Geriatrics Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei 230022, PR China.
BACKGROUND: Phagocytic clearance of apoptotic eosinophils plays an important role in the successful resolution of asthmatic inflammation. To our knowledge, there is limited information available on the effects of anti-asthma drugs on the ingestion of apoptotic eosinophils by bronchial epithelial cells.
AIMS: To evaluate the effects of dexamethasone, aminophylline and terbutaline on the ingestion of apoptotic eosinophils by A549 cells.
METHODS: Eosinophils were purified by CD15 and CD16-dependent immunomagnetic selection from peripheral blood of five normal donors. The capacity of phagocytosis of apoptotic eosinophils by A549 cells were assessed under the microscope. IL-6 and IL-8 released from A549 cells to the culture supernatants were measured by RIA.
RESULTS: Dexamethasone enhanced the phagocytic capacity of A549 cells and inhibited the production of IL-6 and IL-8 from A549 cells stimulated by LPS. Interestingly, aminophylline and terbutaline could not only down-regulate the ingestion of apoptotic eosinophils by A549 cells in a time- and dose-dependent manner, but also decrease IL-6 and IL-8 secretion by A549 cells induced by LPS.
CONCLUSIONS: The present study showed that all of the investigated anti-asthmatic drugs including dexamethasone, aminophylline and terbutaline play an anti-inflammatory effect by decreasing the release of IL-6 and IL-8 induced by LPS. On the other hand, they may have a different effect on the phagocytosis of apoptotic eosinophils by A549 cells, i.e., dexamethasone promotes the uptake of apoptotic eosinophils while aminophylline and terbutaline inhibit the ingestion of apoptotic eosinophils. These results revealed a novel aspect of dexamethasone, aminophylline and terbutaline in the treatment of asthma.
