LPS stimulation of purified human platelets is partly dependent on plasma soluble CD14 to secrete their main secreted product, soluble-CD40-Ligand

BMC Immunology

Hind Hamzeh-Cognasse²  Olivier Garraud¹  Bruno Pozzetto²  Charles-Antoine Arthaud³  Marie-Ange Eyraud³  Fabrice Cognasse³  Pauline Damien² 

[1] Institut National de la Transfusion Sanguine, Paris, France;Université de Lyon, GIMAP-EA3064, 15 rue Ambroise Paré, Saint-Etienne, 42023, France;EFS Auvergne-Loire, Saint-Etienne, France

关键词: TLR4;    Soluble CD14;    Platelet;    Lipopolysaccharide;    Inflammation;    Cytokine;   

Others  :  1126939
DOI  :  10.1186/s12865-015-0067-2

【 摘 要 】

Background

Platelets are instrumental to primary haemostasis; in addition, as they are central to endothelium vascular repair, they play a role in physiological inflammation. Platelets have also been demonstrated to be key players in innate immunity and inflammation, expressing Toll-like receptors (TLRs) to sense microbial infection and initiate inflammatory responses. They are equipped to decipher distinct signals, to use alternate pathways of signalling through a complete signalosome, despite their lack of a nucleus, and to adjust the innate immune response appropriately for pathogens exhibiting different types of ‘danger’ signals. Previous work has described the two main LPS isoforms-TLR4 activation pathways in purified platelets. However, the precise mechanism of TLR4 signalling in platelets is not completely unravelled, especially how this signalling may occur since platelets do not express CD14, the TLR4 pathophysiological companion for LPS sensing. Thus, we investigated from what source the CD14 molecules required for TLR4 signalling in platelets could come.

Results

Here we show that CD14, required for optimal response to LPS stimulation, is obtained from plasma, but used with restrictive regulation. These data add to the body of evidence that platelets are closer to regulatory cells than to first line defenders. The readout of our experiments is the canonical secreted cytokine-like protein, soluble (s)CD40L, a molecule that is central in physiology and pathology and that is abundantly secreted by platelets from the alpha-granules upon stimulation.

Conclusions

We show that sCD14 from plasma contributes to LPS/TLR4 signalling in platelets to allow significant release of soluble CD40L, thereby elucidating the mechanism of LPS-induced platelet responses and providing new insights for reducing LPS toxicity in the circulation.

【 授权许可】

   
2015 Damien et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 3.

【 参考文献 】

• [1]Engelmann B, Massberg S: Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013, 13:34-45.
• [2]Garraud O, Berthet J, Hamzeh-Cognasse H, Cognasse F: Pathogen sensing, subsequent signalling, and signalosome in human platelets. Thromb Res 2011, 127:283-286.
• [3]Sansonetti PJ: To be or not to be a pathogen: that is the mucosally relevant question. Mucosal Immunol 2011, 4:8-14.
• [4]Semple JW, Italiano JE Jr, Freedman J: Platelets and the immune continuum. Nat Rev Immunol 2011, 11:264-274.
• [5]Cognasse F, Payrat JM, Corash L, Osselaer JC, Garraud O: Platelet components associated with acute transfusion reactions: the role of platelet-derived soluble CD40 ligand. Blood 2008, 112:4779-4780.
• [6]Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O’Donnell E, Farndale RW, Ware J, et al.: Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010, 327:580-583.
• [7]Zimmerman GA, Weyrich AS: Immunology: arsonists in rheumatoid arthritis. Science 2010, 327:528-529.
• [8]Vincent JL, Yagushi A, Pradier O: Platelet function in sepsis. Crit Care Med 2002, 30:S313-S317.
• [9]Adelson E, Rheingold JJ, Crosby WH: The platelet as a sponge: a review. Blood 1961, 17:767-774.
• [10]Burkhart JM, Gambaryan S, Watson SP, Jurk K, Walter U, Sickmann A, Heemskerk JW, Zahedi RP: What can proteomics tell us about platelets? Circ Res 2014, 114:1204-1219.
• [11]Berthet J, Damien P, Hamzeh-Cognasse H, Arthaud CA, Eyraud MA, Zeni F, Pozzetto B, McNicol A, Garraud O, Cognasse F: Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokine secretion. Clin Immunol 2012, 145:189-200.
• [12]Shiraki R, Inoue N, Kawasaki S, Takei A, Kadotani M, Ohnishi Y, Ejiri J, Kobayashi S, Hirata K, Kawashima S, et al.: Expression of Toll-like receptors on human platelets. Thromb Res 2004, 113:379-385.
• [13]Cognasse F, Hamzeh H, Chavarin P, Acquart S, Genin C, Garraud O: Evidence of Toll-like receptor molecules on human platelets. Immunol Cell Biol 2005, 83:196-198.
• [14]Spinelli SL, Casey AE, Pollock SJ, Gertz JM, McMillan DH, Narasipura SD, Mody NA, King MR, Maggirwar SB, Francis CW, et al.: Platelets and megakaryocytes contain functional nuclear factor-kappaB. Arterioscler Thromb Vasc Biol 2010, 30:591-598.
• [15]Malaver E, Romaniuk MA, D’Atri LP, Pozner RG, Negrotto S, Benzadon R, Schattner M: NF-kappaB inhibitors impair platelet activation responses. J Thromb Haemost 2009, 7:1333-1343.
• [16]Kappelmayer J, Beke Debreceni I, Vida A, Antal-Szalmas P, Clemetson KJ, Nagy B Jr: Distinct effects of Re- and S-forms of LPS on modulating platelet activation. J Thromb Haemost 2013, 11:775-778.
• [17]Panzer S: Differential response to LPS isotypes induced platelet activation mediated by Toll-like receptor (TLR)-4. Clin Immunol 2013, 146:13-14.
• [18]Guha M, Mackman N: LPS induction of gene expression in human monocytes. Cell Signal 2001, 13:85-94.
• [19]Shashkin PN, Brown GT, Ghosh A, Marathe GK, McIntyre TM: Lipopolysaccharide is a direct agonist for platelet RNA splicing. J Immunol 2008, 181:3495-3502.
• [20]Brown GT, McIntyre TM: Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1beta-rich microparticles. J Immunol 2011, 186:5489-5496.
• [21]Damien P, Cognasse F, Lucht F, Suy F, Pozzetto B, Garraud O, Hamzeh-Cognasse H: Highly active antiretroviral therapy alters inflammation linked to platelet cytokines in HIV-1-infected patients. J Infect Dis 2013, 208:868-870.
• [22]Zhang G, Han J, Welch EJ, Ye RD, Voyno-Yasenetskaya TA, Malik AB, Du X, Li Z: Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J Immunol 2009, 182:7997-8004.
• [23]Andonegui G, Kerfoot SM, McNagny K, Ebbert KV, Patel KD, Kubes P: Platelets express functional Toll-like receptor-4. Blood 2005, 106:2417-2423.
• [24]Brown GT, Narayanan P, Li W, Silverstein RL, McIntyre TM: Lipopolysaccharide stimulates platelets through an IL-1beta autocrine loop. J Immunol 2013, 191:5196-5203.
• [25]Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR: Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation 2002, 106:896-899.
• [26]Lauer S, Kunde YA, Apodaca TA, Goldstein B, Hong-Geller E: Soluble MD2 increases TLR4 levels on the epithelial cell surface. Cell Immunol 2009, 255:8-16.
• [27]Rondina MT, Weyrich AS, Zimmerman GA: Platelets as cellular effectors of inflammation in vascular diseases. Circ Res 2013, 112:1506-1519.