EFhd2/swiprosin-1 regulates LPS-induced macrophage recruitment via enhancing actin polymerization and cell migration.

Macrophage motility is vital in innate immunity, which contributes strategically to the defensive inflammation process. During bacterial infection, lipopolysaccharide (LPS) potently activates the migration of macrophages via the NF-κB/iNOS/c-Src signaling pathway. However, the downstream region of c-Src that participates in macrophage migration is unclear. EFhd2, a novel actin bundling protein, was evaluated for its role in LPS-stimulated macrophage migration in this study. We found that LPS stimulated the up-regulation, tyrosine phosphorylation and membrane translocation of EFhd2 in macrophages. The absence of EFhd2 inhibited the recruitment of macrophages in the lungs of LPS-induced septic mice. LPS-induced macrophage migration was neutralized by the deletion of EFhd2. EFhd2-mediated up-regulation of NFPs (including Rac1/Cdc42, N-WASP/WAVE2 and Arp2/3 complex) induced by LPS could be used to explain the role of EFhd2 in promoting actin polymerization. Furthermore, the purified EFhd2 could directly promote actin polymerization in vitro. Dasatinib, a c-Src specific inhibitor, inhibited the up-regulation of EFhd2 stimulated by LPS. Therefore, our study demonstrated that EFhd2 might be involved in LPS-stimulated macrophage migration, which provides a potential target for LPS-activated c-Src during macrophage mobilization.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}