Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Nat Immunol. 2010 Mar;11(3):232-9. doi: 10.1038/ni.1842. Epub 2010 Jan 31.
Macrophage phagocytosis is critical for defense against pathogens. Whereas many steps of phagocytosis involve ionic flux, the underlying ion channels remain ill defined. Here we show that zymosan-, immunoglobulin G (IgG)- and complement-mediated particle binding and phagocytosis were impaired in macrophages lacking the cation channel TRPV2. TRPV2 was recruited to the nascent phagosome and depolarized the plasma membrane. Depolarization increased the synthesis of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)), which triggered the partial actin depolymerization necessary for occupancy-elicited phagocytic receptor clustering. TRPV2-deficient macrophages were also defective in chemoattractant-elicited motility. Consequently, TRPV2-deficient mice showed accelerated mortality and greater organ bacterial load when challenged with Listeria monocytogenes. Our data demonstrate the participation of TRPV2 in early phagocytosis and its fundamental importance in innate immunity.
巨噬细胞吞噬作用对于防御病原体至关重要。虽然吞噬作用的许多步骤都涉及离子流，但潜在的离子通道仍未明确界定。在这里，我们发现缺乏阳离子通道 TRPV2 的巨噬细胞中，酵母聚糖、免疫球蛋白 G (IgG) 和补体介导的颗粒结合和吞噬作用受损。TRPV2 被募集到新生吞噬体并使质膜去极化。去极化增加了磷脂酰肌醇-4,5-二磷酸 (PtdIns(4,5)P(2)) 的合成，这触发了占据诱导的吞噬受体聚集所必需的部分肌动蛋白解聚。TRPV2 缺陷型巨噬细胞在趋化因子诱导的运动性方面也存在缺陷。因此，当受到李斯特菌单核细胞增生症的挑战时，TRPV2 缺陷型小鼠表现出加速的死亡率和更大的器官细菌负荷。我们的数据表明 TRPV2 参与了早期吞噬作用及其在先天免疫中的基本重要性。
