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Thromb Haemost 2016; 115(03): 632-645
DOI: 10.1160/th15-04-0322
Blood Cells, Inflammation and Infection
Schattauer GmbH

Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFKB signalling pathway in monocytes

Jun-Jie Bei
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
3   Department of Cardiology, Guangxi Provincial Corps Hospital of CAPF, Nanning, Guangxi, China
,
Chuan Liu
2   Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China
,
Song Peng
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
,
Cheng-Hai Liu
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
,
Wei-Bo Zhao
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
,
Xiao-Long Qu
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
,
Qiang Chen
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
,
Zhou Zhou
2   Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China
,
Zheng-Ping Yu
2   Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing, China
,
Karlheinz Peter
4   Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, and Department of Medicine and Immunology, Monash University, Melbourne, Victoria, Australia
,
Hou-Yuan Hu
1   Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
› Author Affiliations Financial support: This study was supported by grants from the National Natural Science Foundation of China (No. 81270362 and No. 81470561) and State Project For Essential Drug Research and Development (No. 2013ZX09103003–001).
Further Information

Publication History

Received: 19 April 2015

Accepted after major revision: 28 October 2015

Publication Date:
20 March 2018 (online)

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Summary

Pathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.

Keywords

Staphylococcal superantigen-like protein 5 - platelet microparticles - monocytes - inflammation - CD40 ligand

Supplementary Material

 

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