|
|
Blood, 15 January 2006, Vol. 107, No. 2, pp. 637-641.
Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-06-2202.
Previous Article | Next Article 
Submitted June 1, 2005
Accepted September 8, 2005
Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor- production in vivo
Rukhsana Aslam, Edwin R Speck, Michael Kim, Andrew R Crow, KW A Bang, Frederick P Nestel, Heyu Ni, Alan H Lazarus, John Freedman, and John W Semple*
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; The Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; Canadian Blood Services, Toronto, Ontario, Canada; The Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada
Faculty of Medicine, McGill University, Montreal, Quebec, Canada
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Canadian Blood Services, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Canada; Department of Medicine, University of Toronto, Canada
* Corresponding author; email: semplej{at}smh.toronto.on.ca.
Toll-like receptors (TLR) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecular patterns (PAMP) on invading microorganisms. Platelets also play a role in innate immunity and we studied whether they may express TLR. Results show that human and murine platelets variably expressed TLR 2, 4 and 9 by flow cytometry and western blotting. TLR4 expression was confirmed by demonstrating murine platelet binding to lipopolysaccharide (LPS). Thrombin activation of the platelets significantly enhanced expression of TLR9 suggesting that at least some TLR may derive from intracellular compartments. When LPS was administered to LPS-sensitive C3H/HeN and LPS-resistant C3H/HeJ mice, functional TLR4 expression in vivo was shown to be responsible for LPS-induced thrombocytopenia. However, when the C3H/HeN mice were first rendered thrombocytopenic by an anti-platelet antibody and then administered LPS, there was a significant reduction in their ability to produce TNF- . The lowered cytokine production in the thrombocytopenic mice was restored upon a platelet transfusion. These results suggest that platelets express various TLR and the functional significance of one of these, TLR4, appears to be a role in modulation of LPS-induced thrombocytopenia and TNF- production. This work implicates platelets as important mediators of innate immune responses against invading microorganisms.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G. Zhang, J. Han, E. J. Welch, R. D. Ye, T. A. Voyno-Yasenetskaya, A. B. Malik, X. Du, and Z. Li
Lipopolysaccharide Stimulates Platelet Secretion and Potentiates Platelet Aggregation via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway
J. Immunol.,
June 15, 2009;
182(12):
7997 - 8004.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Maugeri, P. Rovere-Querini, V. Evangelista, C. Covino, A. Capobianco, M. T. S. Bertilaccio, A. Piccoli, L. Totani, D. Cianflone, A. Maseri, et al.
Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program
Blood,
May 21, 2009;
113(21):
5254 - 5265.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X.-L. Zhang, J. Peng, J.-Z. Sun, J.-J. Liu, C.-S. Guo, Z.-G. Wang, Y. Yu, Y. Shi, P. Qin, S.-G. Li, et al.
De novo induction of platelet-specific CD4+CD25+ regulatory T cells from CD4+CD25- cells in patients with idiopathic thrombocytopenic purpura
Blood,
March 12, 2009;
113(11):
2568 - 2577.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kang, S.-P. Lee, K. E. Kim, H.-Z. Kim, S. Memet, and G. Y. Koh
Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced lymphangiogenesis by chemotactic recruitment of macrophages
Blood,
March 12, 2009;
113(11):
2605 - 2613.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Blair, S. Rex, O. Vitseva, L. Beaulieu, K. Tanriverdi, S. Chakrabarti, C. Hayashi, C. A. Genco, M. Iafrati, and J. E. Freedman
Stimulation of Toll-Like Receptor 2 in Human Platelets Induces a Thromboinflammatory Response Through Activation of Phosphoinositide 3-Kinase
Circ. Res.,
February 13, 2009;
104(3):
346 - 354.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. A. Bozza, A. M. Shah, A. S. Weyrich, and G. A. Zimmerman
Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation
Am. J. Respir. Cell Mol. Biol.,
February 1, 2009;
40(2):
123 - 134.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E Raschi, M. Borghi, C Grossi, V Broggini, S Pierangeli, and P. Meroni
Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome
Lupus,
October 1, 2008;
17(10):
938 - 943.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
P. N. Shashkin, G. T. Brown, A. Ghosh, G. K. Marathe, and T. M. McIntyre
Lipopolysaccharide Is a Direct Agonist for Platelet RNA Splicing
J. Immunol.,
September 1, 2008;
181(5):
3495 - 3502.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. D. Elzey, N. W. Schmidt, S. A. Crist, T. P. Kresowik, J. T. Harty, B. Nieswandt, and T. L. Ratliff
Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge
Blood,
April 1, 2008;
111(7):
3684 - 3691.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Haselmayer, L. Grosse-Hovest, P. von Landenberg, H. Schild, and M. P. Radsak
TREM-1 ligand expression on platelets enhances neutrophil activation
Blood,
August 1, 2007;
110(3):
1029 - 1035.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. Semple, R. Aslam, M. Kim, E. R. Speck, and J. Freedman
Platelet-bound lipopolysaccharide enhances Fc receptor mediated phagocytosis of IgG-opsonized platelets
Blood,
June 1, 2007;
109(11):
4803 - 4805.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Othman, A. Labelle, I. Mazzetti, H. S. Elbatarny, and D. Lillicrap
Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance
Blood,
April 1, 2007;
109(7):
2832 - 2839.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. von Hundelshausen and C. Weber
Platelets as Immune Cells: Bridging Inflammation and Cardiovascular Disease
Circ. Res.,
January 5, 2007;
100(1):
27 - 40.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Jayachandran, G. J. Brunn, K. Karnicki, R. S. Miller, W. G. Owen, and V. M. Miller
In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk
J Appl Physiol,
January 1, 2007;
102(1):
429 - 433.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. Semple, R. Aslam, E. R. Speck, and J. Freedman
Lipopolysaccharide Binds Platelet Toll-Like Receptor 4 and Mediates the Activation of Phagocytes in the Reticuloendothelial System (RES): A Novel Mechanism of Host Immunity.
Blood (ASH Annual Meeting Abstracts),
November 16, 2006;
108(11):
1093 - 1093.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Ware, E. Camerer, K. Welty-Wolf, M. J. Schultz, and M. A. Matthay
Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L307 - L311.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. K. Damas, M. Jensenius, T. Ueland, K. Otterdal, A. Yndestad, S. S. Froland, J.-M. Rolain, B. Myrvang, D. Raoult, and P. Aukrust
Increased Levels of Soluble CD40L in African Tick Bite Fever: Possible Involvement of TLRs in the Pathogenic Interaction between Rickettsia africae, Endothelial Cells, and Platelets
J. Immunol.,
August 15, 2006;
177(4):
2699 - 2706.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A.-l. Stahl, M. Svensson, M. Morgelin, C. Svanborg, P. I. Tarr, J. C. Mooney, S. L. Watkins, R. Johnson, and D. Karpman
Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome
Blood,
July 1, 2006;
108(1):
167 - 176.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Patrignani, C. Di Febbo, S. Tacconelli, V. Moretta, G. Baccante, M. G. Sciulli, E. Ricciotti, M. L. Capone, I. Antonucci, M. D. Guglielmi, et al.
Reduced thromboxane biosynthesis in carriers of toll-like receptor 4 polymorphisms in vivo
Blood,
May 1, 2006;
107(9):
3572 - 3574.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|