TY - JOUR
T1 - Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock
AU - Gibot, Sébastien
AU - Buonsanti, Cecilia
AU - Massin, Frédéric
AU - Romano, Michele
AU - Kolopp-Sarda, Marie Nathalie
AU - Benigni, Fabio
AU - Faure, Gilbert C.
AU - Béné, Marie Christine
AU - Panina-Bordignon, Paola
AU - Passini, Nadia
AU - Lévy, Bruno
PY - 2006/5
Y1 - 2006/5
N2 - The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1β, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.
AB - The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1β, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.
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U2 - 10.1128/IAI.74.5.2823-2830.2006
DO - 10.1128/IAI.74.5.2823-2830.2006
M3 - Article
C2 - 16622220
AN - SCOPUS:33646377861
VL - 74
SP - 2823
EP - 2830
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 5
ER -