Identification of Extracellular Actin As a Ligand for Triggering Receptor Expressed on Myeloid Cells-1 Signaling

Frontiers in Immunology

Lei Fu¹  Anding Zhang¹  Caiyun Xie¹  Shan Pan¹  Meilin Jin¹  Lan Lin¹  Zhi Li¹  Wenke Li²  You Zhou²  Li Han² 

[1] Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan, China;State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China;The Cooperative Innovation Center for Sustainable Pig Production, International Joint Research Center for Animal Disease Control, Wuhan, China;

关键词: sepsis;    triggering receptor expressed on myeloid cells-1;    actin;    ligands;    interaction;    signaling;   

DOI  :  10.3389/fimmu.2017.00917

来源: DOAJ

【 摘 要 】

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions, and it is an essential mediator of death in sepsis. However, the ligand for TREM-1 has not been fully identified. Previous research identified a natural ligand of TREM-1 distributed on platelets that contributed to the development of sepsis. However, the exact signal for TREM-1 recognition remains to be identified. Here, we identified actin as a TREM-1-interacting protein on platelets and found that recombinant actin could interact with recombinant TREM-1 extracellular domain directly. Furthermore, actin co-localized with TREM-1 on the surface of activated mouse macrophage RAW264.7 cells interacting with platelets. In addition, recombinant actin could enhance the inflammatory response of macrophages from wt mice but not from trem1−/− mice, and the enhancement could be inhibited by LP17 (a TREM-1 inhibitor) in a dose-dependent manner. Importantly, extracellular actin showed co-localization with TREM-1 in lung tissue sections from septic mice, which suggested that TREM-1 recognized actin during activation in sepsis. Therefore, the present study identified actin as a new ligand for TREM-1 signaling, and it also provided a link between both essential regulators of death in sepsis.

【 授权许可】

Unknown