Triggering receptor expressed on myeloid cells-1 in neutrophil inflammatory responses: differential regulation of activation and survival.
Polymorphonuclear neutrophils (PMN) are crucial in the innate host defense by their ability to rapidly accumulate in inflamed tissues and clear a site of infection from microbial pathogens by their potent effector mechanisms. The triggering receptor expressed on myeloid cells (TREM)-1 is a recently described activating receptor on PMN with an important role in inflammation. However, the effects of TREM-1 stimulation on a cellular level remain to be further defined. To characterize TREM-1-mediated activation of human PMN, we evaluated the effect of receptor ligation on PMN effector functions. Activation via TREM-1 induces immediate degranulation of neutrophilic granules resulting in the release of IL-8, respiratory burst, and phagocytosis. TREM-1 ligation synergizes with the activation by the Toll-like receptors (TLR) ligands LPS, Pam(3)Cys, and R-848. In contrast, no synergy between TREM-1- and TLR-mediated stimulation was observed concerning PMN survival, whereas TLR-mediated stimuli protect PMN from apoptosis, concurrent TREM-1 activation neutralizes these anti-apoptotic effects. These results give a new perspective for the regulation of neutrophil inflammatory responses emphasizing the importance of TREM-1 in innate immunity.
Radsak
Markus P
MP
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tuebingen, Germany. markus.radsak@uni-tuebingen.de
Salih
Helmut R
HR
Rammensee
Hans-Georg
HG
Schild
Hansjörg
H
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D022423:Myeloid Cells / Q000378:metabolism*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D010587:Phagocytosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016897:Respiratory Burst / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007093:Imidazoles; D008024:Ligands; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; D003545:Cysteine; C402365:resiquimod