Phosphoinositide3-kinase regulates actin polymerization during delayed phagocytosis of Helicobacter pylori
Phosphoinositide3-kinase regulates actin polymerization during delayed phagocytosis of Helicobacter pylori
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DOI：
10.1189/jlb.0205091
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发表时间：
2005-07-01
影响因子：
5.5
通讯作者：
Wittine, LM
中科院分区：
文献类型：
--
作者：
Allen, LAH;Allgood, JA;Wittine, LM
我们以前已经表明，幽门螺杆菌（Hp）的致溃疡（I型）菌株延缓其进入巨噬细胞。然而，调节Hp吞噬作用的信号通路在很大程度上是不确定的。我们发现，Hp在巨噬细胞中强烈激活TA类磷酸肌醇3-激酶（PI 3 Ks），与吞噬作用一致，并且是内源性的; p85和活性蛋白激酶B α在形成吞噬体时积累。PI 3 K抑制剂渥曼青霉素和LY 294002以剂量依赖性方式抑制Hp的吞噬作用，并且吞噬的阻断与附着细菌下方膜中3 '-磷酸肌醇的损失直接相关。在摄取大的免疫球蛋白G（IgG）包被的颗粒，PI 3 Ks调节伪足的延伸和吞噬体关闭。与此形成鲜明对比的是，我们发现3 '-磷酸肌醇在Hp摄取位点调节肌动蛋白聚合。此外，Hp和IgG头部激活不同的PI 3 K亚型。含有IgG包被颗粒的吞噬体积累3 '-磷酸酶和10号染色体上缺失的张力蛋白同源物以及含有Src同源2结构域的肌醇5'-磷酸酶，而Hp吞噬体不积累。最后，快速摄取IgG调理Hp或毒性较低的II型Hp是PI 3 K独立的。我们得出结论，Hp和IgG珠摄入不同的机制和PI 3 Ks调节肌动蛋白细胞骨架在缓慢吞噬溃疡性Hp。
We have shown previously that ulcerogenic (type I) strains of Helicobacter pylori (Hp) retard their entry into macrophages. However, the signaling pathways that regulate Hp phagocytosis are largely undefined. We show here that Hp strongly activated class TA phosphoinositide3-kinases (PI3Ks) in macrophages, coincident with phagocytosis, and endogenous; p85 and active protein kinase B alpha accumulated on forming phagosomes. PI3K inhibitors, wortmannin and LY294002, inhibited phagocytosis of Hp in a dose-dependent manner, and blockade of engulfment correlated directly with loss of 3'-phosphoinositides in the membrane subjacent to attached bacteria. During uptake of large immunoglobulin G (IgG)-coated particles, PI3Ks regulate pseudopod extension and phagosome closure. In marked contrast, we show here that 3'-phosphoinositides regulated actin polymerization at sites of Hp uptake. Moreover, Hp and IgG heads activated distinct PI3K isoforms. Phagosomes containing IgG-coated particles accumulated 3'-phosphatase and tensin homologue deleted on chromosome 10 and Src homology 2 domain-containing inositol 5'-phosphatase, yet Hp phagosomes did not. Finally, rapid uptake of IgG-opsonized Hp or a less-virulent type II Hp was PI3K-independent. We conclude that Hp and IgG beads are ingested by distinct mechanisms and that PI3Ks regulate the actin cytoskeleton during slow phagocytosis of ulcerogenic Hp.