title: A soluble form of LMIR5/CD300b amplifies lipopolysaccharide-induced lethal inflammation in sepsis.
abstract: Leukocyte mono-Ig-like receptor 5 (LMIR5, also called CD300b) is an activating receptor expressed in myeloid cells. We have previously demonstrated that T cell Ig mucin 1 works as a ligand for LMIR5 in mouse ischemia/reperfusion injury of the kidneys. In this article, we show that LMIR5 is implicated in LPS-induced sepsis in mice. Notably, neutrophils constitutively released a soluble form of LMIR5 (sLMIR5) through proteolytic cleavage of surface LMIR5. Stimulation with TLR agonists augmented the release of sLMIR5. LPS administration or peritonitis induction increased serum levels of sLMIR5 in mice, which was substantially inhibited by neutrophil depletion. Thus, neutrophils were the main source of LPS-induced sLMIR5 in vivo. On the other hand, i.p. administration of LMIR5-Fc, a surrogate of sLMIR5, bound to resident macrophages (M) and stimulated transient inflammation in mice. Consistently, LMIR5-Fc induced in vitro cytokine production of peritoneal M via its unknown ligand. Interestingly, LMIR5 deficiency profoundly reduced systemic cytokine production and septic mortality in LPS-administered mice, although it did not affect in vitro cytokine production of LPS-stimulated peritoneal M. Importantly, the resistance of LMIR5-deficient mice to LPS- or peritonitis-induced septic death was decreased by LMIR5-Fc administration, implicating sLMIR5 in LPS responses in vivo. Collectively, neutrophil-derived sLMIR5 amplifies LPS-induced lethal inflammation.
authors: Division of Cellular Therapy, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;
authors: Yoshinori
authors: Y
authors: Yamanishi
authors: Mariko
authors: M
authors: Takahashi
authors: Kumi
authors: K
authors: Izawa
authors: Masamichi
authors: M
authors: Isobe
authors: Shinichi
authors: S
authors: Ito
authors: Akiho
authors: A
authors: Tsuchiya
authors: Akie
authors: A
authors: Maehara
authors: Ayako
authors: A
authors: Kaitani
authors: Tomoyuki
authors: T
authors: Uchida
authors: Katsuhiro
authors: K
authors: Togami
authors: Yutaka
authors: Y
authors: Enomoto
authors: Fumio
authors: F
authors: Nakahara
authors: Toshihiko
authors: T
authors: Oki
authors: Masunori
authors: M
authors: Kajikawa
authors: Hiroki
authors: H
authors: Kurihara
authors: Toshio
authors: T
authors: Kitamura
authors: Jiro
authors: J
authors: Kitaura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology*; D012995:Solubility; D014162:Transfection
chemical_list: D016207:Cytokines; C527073:LMIR5 protein, mouse; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic