Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection.
Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection.
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DOI：
10.3389/fimmu.2021.702156
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wong WF
中科院分区：
文献类型：
--
作者：
Cheok YY;Tan GMY;Fernandez KC;Chan YT;Lee CYQ;Cheong HC;Looi CY;Vadivelu J;Abdullah S;Wong WF
泊多拉宁(Pdpn)是一种粘蛋白类跨膜蛋白，参与淋巴管生成、血小板聚集和肿瘤转移等多种生理过程。在这里，我们报告了在静息的小鼠单核巨噬细胞RAW264.7细胞中没有Pdpn的转录表达；有趣的是，在幽门螺杆菌或脂多糖刺激下激活的巨噬细胞中观察到Pdpn的显著上调。Pdpn基因敲除的巨噬细胞表现出与野生型相似的完整的吞噬和细胞内杀菌活性，但由于丝状足的形成减弱而表现出移动障碍。相反，Pdpn的异位表达增加了激活的巨噬细胞中的丝状足突。纳米串分析揭示了丝蛋白C基因与Pdpn的存在密切相关，突出了丝蛋白C参与了肌动蛋白聚合活性的调节，而肌动蛋白聚合活性控制着细胞丝状伪足的形成和迁移。此外，在没有Pdpn的情况下，IL-1β的产生显著下降，这表明Pdpn除了在细胞迁移之外，还在Hp感染期间的炎症反应中发挥作用。总之，我们的发现揭开了调节活跃巨噬细胞运动的PDPN网络。
Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1β production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.
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影响因子：
3.4
作者：
Assao, Agnes;Nonogaki, Suely;Oliveira, Denise Tostes
通讯作者：
Oliveira, Denise Tostes
影响因子：
3.7
作者：
Del Rey MJ;Faré R;Izquierdo E;Usategui A;Rodríguez-Fernández JL;Suárez-Fueyo A;Cañete JD;Pablos JL
通讯作者：
Pablos JL
影响因子：
6
作者：
Kunita, Akiko;Kashima, Takeshi G.;Fujita, Naoya
通讯作者：
Fujita, Naoya
DOI：
10.1046/j.1440-1746.1999.01810.x
发表时间：
1999-01-01
影响因子：
4.1
作者：
Kusugami, K;Ando, T;Kaneko, H
通讯作者：
Kaneko, H
影响因子：
15.9
作者：
Maruyama, K;Li, M;Streilein, JW
通讯作者：
Streilein, JW