Abstract
TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-α, MCP-1 and IFN-γ. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B7-2 Antigen / genetics
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Bacteremia / genetics
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Bacteremia / metabolism*
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Bacteremia / microbiology
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Blood Platelets / metabolism
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CD40 Antigens / genetics
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Chemokine CCL2 / metabolism
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Inflammation Mediators / metabolism*
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Interferon-gamma / metabolism
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Interleukin-1beta / metabolism
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Leukocytes / metabolism
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Lymphocytes / metabolism
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Macrophages, Peritoneal / metabolism
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Male
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred BALB C
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Neutrophils / metabolism
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Peritonitis / genetics
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Peritonitis / metabolism
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Phagocytosis
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Pseudomonas Infections / genetics
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Pseudomonas Infections / metabolism*
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Pseudomonas Infections / therapy
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Pseudomonas aeruginosa / isolation & purification*
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Receptors, Immunologic / antagonists & inhibitors*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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Signal Transduction
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Triggering Receptor Expressed on Myeloid Cells-1
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Tumor Necrosis Factor-alpha / metabolism
Substances
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B7-2 Antigen
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CD40 Antigens
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Ccl2 protein, mouse
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Chemokine CCL2
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Inflammation Mediators
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Interleukin-1beta
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Membrane Glycoproteins
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Receptors, Immunologic
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Recombinant Fusion Proteins
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TREM1 protein, mouse
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Triggering Receptor Expressed on Myeloid Cells-1
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Tumor Necrosis Factor-alpha
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Interferon-gamma