title: Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFκB signalling pathway in monocytes.
abstract: 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 NFκB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFκB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Bei
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Peng
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Zhao
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Qu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Yu
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.affiliation: Hou-Yuan Hu, Department of Cardiology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China, Tel.: +86 23 68765167, Fax: +86 23 65317511, E-mail: houyuanhu@hotmail.com.
authors.forename: Hou-Yuan
authors.initials: HY
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus; D001426:Bacterial Proteins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D002465:Cell Movement; D055252:Cell-Derived Microparticles; D018932:Chemokine CCL2 / Q000378:metabolism; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013211:Staphylococcus aureus; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C111835:CCL2 protein, human; D019013:CD40 Antigens; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C000614070:SSL5 protein, Staphylococcus aureus; D048029:TNF Receptor-Associated Factor 6; C000604754:Tifab protein, human; D014409:Tumor Necrosis Factor-alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: CD40 ligand; Staphylococcal superantigen-like protein 5; inflammation; monocytes; platelet microparticles