title: Involvement of Gr-1 dull+ cells in the production of TNF-α and IL-17 and exacerbated systemic inflammatory response caused by lipopolysaccharide.
abstract: Systemic inflammatory response syndrome (SIRS) is a life-threatening disease. Recent reports have demonstrated that the immunoregulatory cells that express Gr-1, a granulocyte surface antigen, play a critical role in various pathological conditions. In the present study, we have established a mouse model of SIRS and addressed the possible contribution of Gr-1+ cells in this model. C57BL/6 mice were injected intraperitoneally with anti-Gr-1 mAb or control IgG 1 day before administration of lipopolysaccharide (LPS). All of the mice that received anti-Gr-1 mAb and LPS died early as a result of hypothermia and severe emaciation, whereas mice treated with control IgG and LPS survived the observation period. In mice treated with anti-Gr-1 mAb and LPS, acute inflammatory changes with alveolar hemorrhage were observed in the lung and proximal convoluted tubule necrosis was observed in the kidney. Serum TNF-α and IL-17A levels were markedly increased in anti-Gr-1 mAb-pretreated mice compared with those in control IgG-treated mice at 1 and 3 h after LPS administration, respectively. Flow cytometric analysis revealed an increase in TNF-α and IL-17A expression in Gr-1 dull+ cells in the peripheral blood mononuclear cells. Neutralization of TNF-α by a specific mAb almost completely reversed the clinical course and inhibited the increased production of IL-17A. In addition, IL-17A KO mice were less susceptible to the lethality in this model. Thus, we established a mouse model of severe SIRS and suggested that Gr-1 dull+ cells may play a critical role in the development of this pathological condition.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tanno
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Akahori
authors.forename: Masahiko
authors.initials: M
authors.lastname: Toyama
authors.forename: Ko
authors.initials: K
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kudo
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Abe
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Emi
authors.initials: E
authors.lastname: Kanno
authors.forename: Ryoko
authors.initials: R
authors.lastname: Maruyama
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kushimoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D007074:Immunoglobulin G / Q000008:administration & dosage; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C503133:Gr-1 protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha
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