TREM-1 ligand expression on platelets enhances neutrophil activation.
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.
Haselmayer
Philipp
P
Institute of Immunology, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.
Grosse-Hovest
Ludger
L
von Landenberg
Philipp
P
Schild
Hansjörg
H
Radsak
Markus P
MP
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism*; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D019087:Selectins / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D016023:Integrins; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D019087:Selectins; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1