title: Effects of the TREM 1 pathway modulation during hemorrhagic shock in rats.
abstract: The triggering receptor expressed on myeloid cells (TREM) 1, a receptor expressed on the surface of neutrophils and monocytes/macrophages, synergizes with the Toll-like receptors in amplifying the inflammatory response mediated by microbial components. Because the pathogenesis of severe blood loss-induced excessive inflammation and multiple organ failure implies leukocyte activation and bacterial translocation, we hypothesized that the TREM-1 pathway modulation would prove beneficial in this setting. Wistar rats were subjected to a 1-h period of hemorrhagic shock and then reperfused with shed blood and ringer lactate for 1 h. At the time of reperfusion, animals were administered with LP17 (a synthetic soluble TREM-1 decoy receptor), a control peptide, or a vehicle (isotonic sodium chloride solution). Plasma concentration of TNF-alpha, IL-6, and soluble TREM-1 were measured by enzyme-linked immunosorbent assay. Lung permeability was assessed by the weight-dry ratio and fluorescein isothiocyanate-labeled albumin lung-blood ratio. Organ dysfunction was appreciated by measuring plasma aspartate aminotransferase and urea concentrations. Bacterial translocation was estimated by blood, mesenteric lymph nodes, and spleens culture. Hemorrhagic shock associated with cardiovascular collapse, lactic acidosis, systemic inflammatory response, and organ dysfunction that was partly prevented by LP17 administration. Hemorrhagic shock induced a marked increase in lung permeability that was also prevented by TREM-1 modulation. Finally, LP17 improved survival. Thus, the early modulation of the TREM-1 pathway by means of a synthetic peptide may be useful during severe hemorrhagic shock in rats in preventing organ dysfunction and improving survival.
authors.affiliation: Groupe Choc, Contrat AVENIR INSERM, Faculté de Médecine, Nancy Université, Nancy, France. s.gibot@chu-nancy.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Massin
authors.forename: Corentine
authors.initials: C
authors.lastname: Alauzet
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.forename: Chantal
authors.initials: C
authors.lastname: Montemont
authors.forename: Solene
authors.initials: S
authors.lastname: Collin
authors.forename: Sophie
authors.initials: S
authors.lastname: Fremont
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy