Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

Triggering receptor expressed on myeloid cells 1 (TREM‐1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM‐1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM‐1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM‐1 expression by MSU crystal–stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air‐pouch model of crystal‐induced acute inflammation was determined. The biologic role of TREM‐1 in crystal‐induced cytokine production by resident peritoneal macrophages was also investigated.

TREM‐1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air‐pouch model was determined by quantitative real‐time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti–TREM‐1 agonist antibody was determined by enzyme‐linked immunosorbent assay.

TREM‐1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM‐1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti–TREM‐1 agonist antibody synergistically increased the production of both interleukin‐1β and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM‐1 expression in infiltrating leukocytes in a murine air‐pouch model of crystal‐induced acute inflammation.

These findings suggest that rapid induction of TREM‐1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses.