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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.


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Submitted June 1, 2005
Accepted September 8, 2005

Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-{alpha} 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-{alpha}. 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-{alpha} production. This work implicates platelets as important mediators of innate immune responses against invading microorganisms.


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