Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / physiology
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Antibodies, Monoclonal / pharmacology
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Apoptosis / immunology
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Cell Degranulation / immunology
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Cell Survival / immunology
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Cysteine / analogs & derivatives*
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Cysteine / metabolism
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Humans
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Imidazoles / metabolism
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Ligands
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Lipopolysaccharides / metabolism
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Lipoproteins / metabolism
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Myeloid Cells / metabolism*
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Neutrophil Activation / immunology*
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Neutrophils / immunology
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Neutrophils / metabolism*
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Neutrophils / pathology*
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Phagocytosis / immunology
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Receptors, Cell Surface / metabolism
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Receptors, Cell Surface / physiology
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Receptors, Immunologic / physiology*
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Respiratory Burst / immunology
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Signal Transduction / immunology
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Toll-Like Receptors
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Triggering Receptor Expressed on Myeloid Cells-1
Substances
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Adjuvants, Immunologic
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Antibodies, Monoclonal
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Imidazoles
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Ligands
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Lipopolysaccharides
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Lipoproteins
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Immunologic
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TREM1 protein, human
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Toll-Like Receptors
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Triggering Receptor Expressed on Myeloid Cells-1
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2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine
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Cysteine
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resiquimod