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


METHODS
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.


RESULTS
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-1beta 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.


CONCLUSIONS
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.
Murakami
Yousuke
Y
Kitasato University School of Medicine, Kanagawa, Japan.
Akahoshi
Tohru
T
Hayashi
Izumi
I
Endo
Hirahito
H
Kawai
Shinichi
S
Inoue
Matsuhisa
M
Kondo
Hirobumi
H
Kitasato
Hidero
H
D000208:Acute Disease; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D003460:Crystallization; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014527:Uric Acid / Q000494:pharmacology*
D019138:Antibodies, Blocking; D016207:Cytokines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C471763:Treml1 protein, mouse; D014527:Uric Acid