Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1
Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1
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DOI：
10.4049/jimmunol.168.8.4034
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发表时间：
2002-04-15
影响因子：
4.4
通讯作者：
Karlsson, A
中科院分区：
文献类型：
--
作者：
Almkvist, J;Dahlgren, C;Karlsson, A
半乳糖凝集素是一组广泛分布于自然界的乳糖结合蛋白。到目前为止，已经鉴定了12种哺乳动物半乳糖凝集素，但它们的功能在很大程度上是未知的。在这项工作中，我们研究半乳糖凝集素-1在其与人类中性粒细胞的相互作用，关于细胞表面结合和激活的超氧化物产生NADPH氧化酶。我们表明，半乳糖凝集素-1是能够激活中性粒细胞NADPH氧化酶，只要细胞已经从血液外渗到组织，激活模式是类似的半乳糖凝集素-3。使用体外引发方案，发现半乳糖凝集素-1响应性与颗粒动员和半乳糖凝集素-1与细胞的结合相关，表明存在颗粒定位的受体，其在引发后上调至细胞表面。通过半乳糖凝集素-1覆盖分级的中性粒细胞，我们确定了潜在的半乳糖凝集素-1受体候选人定位在膜的分泌囊泡和明胶酶颗粒。比较了半乳糖凝集素-1和半乳糖凝集素-3与中性粒细胞蛋白的结合，以及两种凝集素激活的剂量依赖性。结果表明，尽管两种半乳糖凝集素之间存在相似性，但它们似乎使用不同的受体激活NADPH氧化酶。总之，半乳糖凝集素-1似乎具有促炎功能，通过激活中性粒细胞呼吸爆发介导。
Galectins are a group of lactose-binding proteins widely distributed in nature. Twelve mammalian galectins have so far been identified, but their functions are to a large extent unknown. In this work we study galectin-1 in its interaction with human neutrophils, with regard to both cell surface binding and activation of the superoxide-producing NADPH-oxidase. We show that galectin-1 is able to activate the neutrophil NADPH-oxidase, provided that the cells have been primed by extravasation from the blood into the tissue, an activation pattern that is similar to that of galectin-3. Using In vitro priming protocols, the galectin-1 responsiveness was found to correlate to granule mobilization and galectin-1 binding to the cells, suggesting the presence of granule-localized receptors that are up-regulated to the cell surface upon priming. By galectin-1 overlay of fractionated neutrophils we identified potential galectin-1 receptor candidates localized in the membranes of the secretory vesicle and gelatinase granules. The binding of galectin-1 and galectin-3 to neutrophil proteins was compared, as were the dose dependencies for activation by the two lectins. The results suggest that, although similarities are found between the two galectins, they appear to activate the NADPH-oxidase using different receptors. In conclusion, galectin-1 appears to have proinflammatory functions, mediated through activation of the neutrophil respiratory burst.