Decrease of vascular endothelial growth factor in macrophages from long-term smokers
Decrease of vascular endothelial growth factor in macrophages from long-term smokers
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DOI：
10.1183/09031936.05.00110504
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发表时间：
2005-04-01
影响因子：
24.3
通讯作者：
Nishimura, M
中科院分区：
文献类型：
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作者：
Nagal, K;Betsuyaku, T;Nishimura, M
血管内皮生长因子（VEGF）是内皮细胞的生存因子和血管生成的启动子，据报道在肺泡巨噬细胞（AMs）中表达。为了研究长期吸烟是否会影响血管内皮生长因子的表达，我们对18名年轻和23名有不同吸烟史的老年志愿者进行了支气管肺泡灌洗（BAL）。实时荧光定量pcr检测AMs中VEGF及其功能受体fms样酪氨酸激酶(Fit)-1的表达，ELISA检测BAL液中VEGF水平。在老年受试者中，当前吸烟者的血管内皮生长因子mRNA比不吸烟者减少1.8倍，此外，在肺气肿患者中，血管内皮生长因子mRNA减少1.5倍，尽管在年轻受试者中，当前吸烟者和不吸烟者之间没有差异。VEGF121和VEGF165亚型的大量减少支持了总VEGF mRNA的下调。然而，相比之下，Flt-1在老年组中没有差异，而在年轻的吸烟者中，与年龄匹配的非吸烟者相比，Flt-1表达上调。无论年龄如何，当前吸烟者与非吸烟者相比，BAL液中的VEGF显著降低。总之，这些数据表明，在有长期吸烟史的老年吸烟者中，血管内皮生长因子在肺泡巨噬细胞中的生物有效性受损。
Vascular endothelial growth factor (VEGF), a survival factor for endothelial cells and a promoter of angiogenesis, is reportedly expressed in alveolar macrophages (AMs).To investigate whether long-term smoking with age affects VEGF expression in AMs, bronchoalveolar lavage (BAL) was performed on 18 young and 23 older volunteers with various smoking histories. The expressions of VEGF and its functional receptor, fms-like tyrosine kinase (Fit)-1, were quantified in AMs by real-time RT-PCR and, further, the level of VEGF in BAL fluid was determined by ELISA.VEGF mRNA in AMs demonstrated a 1.8-fold reduction in current smokers compared with nonsmokers in older subjects and, furthermore, a 1.5-fold downregulation in those with emphysema, although there was no difference between current smokers and nonsmokers, among the young subjects. The downregulation in total VEGF mRNA was supported by the substantial reduction of VEGF121 and VEGF165 isoforms. However, in contrast, Flt-1 mill did not differ within the older groups, whereas it was upregulated in young current smokers compared with age-matched nonsmokers. VEGF in BAL fluid is significantly decreased in current smokers compared with nonsmokers, regardless of their age.In conclusion, these data imply that the biological availability of vascular endothelial growth factor in alveolar macrophages is impaired in older current smokers with long-term smoking histories.