N-Acylhomoserine lactones are potent neutrophil chemoattractants that act via calcium mobilization and actin remodeling

Journal of Leukocyte Biology

Farah Musse¹  Elena Vikström¹  Thommie Karlsson¹  Karl-Eric Magnusson¹ 

[1] Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

关键词: quorum sensing;    migration;    Ca²⁺;    PLC;    Rho-GTPases;    cytoskeleton;   

DOI  :  10.1189/jlb.0111034

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

In gram-negative bacteria, cell-cell communication based on HSL QS molecules is known to coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human immune cell behavior. Using a Transwell migration assay, we found that human primary neutrophils are strongly stimulated by 3O-C12-HSL and -C10-HSL but not C4-HSL in a concentration-dependent manner. Moreover, 3O-C12-HSL and -C10-HSL activate PLCγ1 but not -γ2, mobilize intracellular calcium, and up-regulate IP3R. These changes were paralleled by F-actin accumulation, primarily in the leading edge of neutrophils, as evidenced by phalloidin staining and confocal microscopy. F- and G-actin isolation and quantification by immunoblotting revealed that the F/G-actin ratio was increased significantly after treatment with all three HSLs. Furthemore, 3O-C12-HSL- and 3O-C10-HSL treatment resulted in phosphorylation of Rac1 and Cdc42. In contrast, C4-HSL had negligible influence on the phosphorylation status of PLC and Rac1/Cdc42 and failed to attract neutrophils and induce calcium release. The calcium inhibitor thapsigargin, which blocks ER calcium uptake, strongly prevented neutrophil migration toward 3O-C12-HSL and -C10-HSL. These findings show that the bacterial QS molecules 3O-C12-HSL and -C10-HSL may attract human neutrophils to the sites of bacterial infection and developing biofilms. Indeed, recognition of HSL QS signals by neutrophils may play a critical role in their recruitment during infections.

【 授权许可】

Unknown