Surface and soluble triggering receptor expressed on myeloid cells-1:: Expression patterns in murine sepsis

Objective: To examine the expression patterns of the triggering receptor expressed on myeloid cells (TREM)-1 during experimental septic shock. Design: Animal study. Setting: Animal research laboratory. Subjects: Male BALB/c mice, 7-9 wks of age. Interventions. Septic shock was induced by cecal ligation and puncture in eight mice. Eight additional animals were sham-operated and served as a control group. All animals were resuscitated by fluid infusion and administered antibiotics. Kill was performed under anesthesia 12, 24, or 48 hrs later. Measurements and Main Results. Surface expression of TREM-1 was analyzed using flow cytometry on peripheral blood cells, peritoneal macrophages and neutrophils, splenic macrophages, and Kupffer cells. Gene expression was also studied in these same cells using reverse transcription-polymerase chain reaction. Tumor necrosis factor-alpha, interleukin-1 beta, and soluble TREM-1 concentrations were determined in plasma and peritoneal lavage fluid. Sepsis strongly induced TREM-1 gene expression, which translated into an up-regulation of TREM-11 surface expression on neutrophils and monocytes/macrophages both at the focus on infection as well as distally. Moreover, sepsis induced the release of significant levels of soluble TREM-1. Plasma soluble TREM-1 concentrations negatively correlated with tumor necrosis factor-alpha and interleukin-1 beta levels at 12 hrs. Conclusions. These results provide new information as to the regulation of TREM-1 during sepsis. Considering that both cell-surface and soluble TREM-1 were strongly up-regulated during infection, this study may add support to the putative usefulness of TREM-1 as a diagnostic tool.