Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection.
Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection.
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DOI：
10.1371/journal.pone.0004891
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Kannan S;Huang H;Seeger D;Audet A;Chen Y;Huang C;Gao H;Li S;Wu M
尽管肺泡上皮II型细胞（AECII）在维持肺泡完整性方面发挥着重要作用，但它们对免疫防御的贡献程度知之甚少。在这里，我们证明AECII激活肺泡巨噬细胞（AM）功能，如使用由铜绿假单胞菌感染的AECII的条件培养基进行吞噬。aecii衍生的趋化因子MCP-1是一种单核细胞趋化蛋白，被认为是增强AM功能的主要因素。我们认为AECII增强的免疫效力可能在减轻细菌繁殖和肺炎中起关键作用。MCP-1中和抗体降低AM的吞噬和超氧化物释放能力。此外，MCP-1−/−小鼠在感染PAO1和PAK的情况下，与wt窝友相比，细菌负担增加。与对照组相比，MCP-1−/−小鼠的AM也表现出更少的超氧化物和受损的吞噬功能。此外，AECII条件培养基通过激活AM功能增加MCP-1−/−小鼠气道的宿主防御。在机制上，我们发现Lyn介导的NFκB活化导致MCP-1基因表达和分泌增加。因此，Lyn - / -小鼠减少了MCP-1的分泌，导致AM的超氧化物和吞噬作用减少。总的来说，我们的数据表明AECII可以作为对抗细菌感染的免疫增强剂，特别是在严重的免疫功能低下的情况下。
Although alveolar epithelial type II cells (AECII) perform substantial roles in the maintenance of alveolar integrity, the extent of their contributions to immune defense is poorly understood. Here, we demonstrate that AECII activates alveolar macrophages (AM) functions, such as phagocytosis using a conditioned medium from AECII infected by P. aeruginosa. AECII-derived chemokine MCP-1, a monocyte chemoattractant protein, was identified as a main factor in enhancing AM function. We proposed that the enhanced immune potency of AECII may play a critical role in alleviation of bacterial propagation and pneumonia. The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies. Furthermore, MCP-1−/− mice showed an increased bacterial burden under PAO1 and PAK infection vs. wt littermates. AM from MCP-1−/− mice also demonstrated less superoxide and impaired phagocytosis over the controls. In addition, AECII conditioned medium increased the host defense of airway in MCP-1−/− mice through the activation of AM function. Mechanistically, we found that Lyn mediated NFκB activation led to increased gene expression and secretion of MCP-1. Consequently Lyn−/− mice had reduced MCP-1 secretion and resulted in a decrease in superoxide and phagocytosis by AM. Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.
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Fcgamma受体介导的巨噬细胞中缺乏SRC家族酪氨酸激酶HCK，FGR和Lyn的吞噬作用。
影响因子：
15.3
作者：
Fitzer-Attas, C J;Lowry, M;Crowley, M T;Finn, A J;Meng, F;DeFranco, A L;Lowell, C A
通讯作者：
Lowell, C A
影响因子：
5.4
作者：
Kannan, Shibichakravarthy;Audet, Aaron;Wu, Min
通讯作者：
Wu, Min
DOI：
10.1164/rccm.200311-1521oc
发表时间：
2004-12-01
影响因子：
24.7
作者：
Drannik, AG;Pouladi, MA;Stämpfli, MR
通讯作者：
Stämpfli, MR
影响因子：
4.4
作者：
Lo, Bernice;Hansen, Soren;Wright, Jo Rae
通讯作者：
Wright, Jo Rae
影响因子：
3.1
作者：
Miyata, S;Casey, M;Drenkard, E
通讯作者：
Drenkard, E