Involvement of Gr-1dull+ cells in the production of TNF-α and IL-17 and exacerbated systemic inflammatory response caused by lipopolysaccharide

Daiki Tanno, Yukiko Akahori, Masahiko Toyama, Ko Sato, Daisuke Kudo, Yuzuru Abe, Tomomitsu Miyasaka, Hideki Yamamoto, Keiko Ishii, Emi Kanno, Ryoko Maruyama, Shigeki Kushimoto, Yoichiro Iwakura, Kazuyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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-1dull+ 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-1dull+ cells may play a critical role in the development of this pathological condition.

Original languageEnglish
Pages (from-to)186-195
Number of pages10
Issue number1
Publication statusPublished - 2014 Feb


  • Gr-1
  • Lipopolysaccharide
  • Mice
  • Systemic inflammatory response syndrome (SIRS)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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