Molecular mechanisms of HGF-beta-induced macrophage phagocytosis

我们提供的证据表明，肝细胞生长因子(HGF)β链残留物(HGF-β)通过与甘露糖受体(MR)结合而有效地刺激中性粒细胞吞噬凋亡的中性粒细胞，甘露糖受体是新近发现的HGF-β受体。HGF-β与肌动蛋白结合后，可能通过肌动蛋白结合蛋白IQGAP1与肌动蛋白结合蛋白IQGAP1相互作用，调节肌动蛋白细胞骨架，增强吞噬功能。HGF-β还诱导CD11b的表面表达，CD11b是补体介导的吞噬作用所需的受体复合体的组成部分。提示HGF-β/MR轴诱导的巨噬细胞吞噬功能可阻止中性粒细胞的凋亡聚集和炎性分子的释放，从而减轻炎症反应，促进组织修复。

We provide evidence that hepatocyte growth factor (HGF) beta-chain remnant (HGF-beta), generated through fragmentation of HGF by proteases released from inflammatory cells such as neutrophils, potently stimulated phagocytosis of apoptotic neutrophils by binding to mannose receptor (MR), which recently identified as an HGF-beta receptor. Upon binding to MR, HGF-beta may modulate actin cytoskeleton and enhance phagocytosis through interaction between MR and actin-binding protein IQGAP1. HGF-beta also induced surface expression of CD11b, a component of receptor complex required for complement-mediated phagocytosis. These findings suggest that HGF-beta/MR axis-induced macrophage phagocytosis could prevent accumulation of apoptotic neutrophils and release of inflammatory molecules from neutrophils, which leads to resolution of inflammation and promotion of tissue repair.