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 Blood, 1 August 2007, Vol. 110, No. 3, pp. 1029-1035.
Prepublished online as a Blood First Edition Paper on April 23, 2007; DOI 10.1182/blood-2007-01-069195.

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PHAGOCYTES

TREM-1 ligand expression on platelets enhances neutrophil activation

Philipp Haselmayer1, Ludger Grosse-Hovest2, Philipp von Landenberg3, Hansjörg Schild1, and Markus P. Radsak1,4

1 Institute of Immunology, University of Mainz, Mainz; 2 Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen; 3 Department of Clinical Chemistry, University Hospital, Johannes Gutenberg-University, Mainz; 4 IIIrd Department of Medicine, University Hospital, Johannes Gutenberg-University, Mainz, Mainz, Germany

The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leukocyte (PMN) effector functions (provoked by LPS). However, TREM-1 interaction with its ligand is not required for platelet/PMN complex formation, which is dependent on integrins and selectins. Taken together, the results indicate that the TREM-1 ligand is expressed by platelets, and the TREM-1/ligand interaction contributes to the amplification of LPS-induced PMN activation. Our results shed new light on our understanding of TREM-1 and its role in the innate inflammatory response in infections and might contribute to the development of future concepts to treat sepsis.


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Platelets and leukocytes: aggregate knowledge
Alan D. Michelson and Peter E. Newburger
Blood 2007 110: 794-795. [Full Text] [PDF]



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