Cholesterol-rich membrane rafts and Lyn are involved in phagocytosis during pseudomonas aeruginosa infection
Cholesterol-rich membrane rafts and Lyn are involved in phagocytosis during pseudomonas aeruginosa infection
复制标题
DOI：
10.4049/jimmunol.180.4.2396
复制
发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Wu, Min
中科院分区：
文献类型：
--
作者：
Kannan, Shibichakravarthy;Audet, Aaron;Wu, Min
病原体的吞噬机制仍有待充分表征。我们报告了一种新的铜绿假单胞菌的吞噬途径，它是由富含胆固醇的膜筏启动，并依赖于林恩，主要是一种免疫调节剂，具有积极和消极的作用。阻断林恩或阻断胆固醇合成显著抑制肺泡巨噬细胞的吞噬作用。我们发现林恩通过Src同源2和3结构域结合并激活PI3 K和Akt以调节吞噬的铜绿假单胞菌的细胞内路线。进一步分析表明，林恩和筏组分进入吞噬体和晚期溶酶体。最后，呼吸爆发依赖于林恩和膜筏，证实了小干扰RNA和显性负策略。我们的研究表明，林恩沿着膜筏在肺泡巨噬细胞的吞噬作用在感染过程中发挥了重要作用。
The mechanism of phagocytosis of pathogens remains to be fully characterized. We report a novel phagocytosis pathway for Pseudomonas aeruginosa, which is initiated by cholesterol-rich membrane rafts and is dependent on Lyn, primarily an immune regulator with both positive and negative roles. Blocking of Lyn or blocking of cholesterol synthesis significantly inhibited phagocytosis by alveolar macrophages. We found that Lyn, via Src homology 2 and 3 domains, bound to and then activated PI3K and Akt to regulate intracellular routing of the engulfed P. aeruginosa. Further analysis indicates that Lyn and raft components entered in phagosomes and late lysosomes. Finally, respiratory burst was dependent on Lyn and membrane rafts, as confirmed by small interfering RNA and dominant-negative strategies. Our investigations demonstrate that Lyn along with membrane rafts plays a fundamental role in phagocytosis by alveolar macrophages during infection.