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Inflammation

, Volume 37, Issue 1, pp 186–195 | Cite as

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 KawakamiEmail author
Article
  • 314 Downloads

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-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.

KEY WORDS

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

Notes

Acknowledgments

The authors thank Dr. Fujiro Sendo (Yamagata University, Yamagata, Japan) and Dr. Akio Nakane (Hirosaki University Graduate School of Medicine, Hirosaki, Japan) for their kind gifts of anti-Gr-1 mAb and anti-TNF-α mAb, respectively. This work was supported in part by a Grant from the Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Challenging Exploratory Research (23659841)) and a Grant from the Ministry of Health, Labor and Welfare of Japan (Research on Emerging and Re-emerging Infectious Diseases; 22-SHINKOU-IPPAN-014).

Conflict of interest

The authors declare that they have no financial conflicts of interest.

Supplementary material

10753_2013_9729_MOESM1_ESM.ppt (82 kb)
Fig. S1 Effect of anti-Gr-1 mAb on the expression of Gr-1 on PBMC. Mice were treated with rat IgG or anti-Gr-1 mAb, and 24 h later, PBMC were stained with anti-Gr-1 mAb and analyzed using a flow cytometry. Dotted line, rat IgG-treated; shaded area, anti-Gr-1 mAb-treated. (PPT 82 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Daiki Tanno
    • 1
    • 2
  • Yukiko Akahori
    • 1
    • 3
  • Masahiko Toyama
    • 1
  • Ko Sato
    • 1
  • Daisuke Kudo
    • 4
  • Yuzuru Abe
    • 1
    • 5
  • Tomomitsu Miyasaka
    • 1
    • 6
  • Hideki Yamamoto
    • 1
  • Keiko Ishii
    • 1
  • Emi Kanno
    • 7
  • Ryoko Maruyama
    • 7
  • Shigeki Kushimoto
    • 4
  • Yoichiro Iwakura
    • 8
  • Kazuyoshi Kawakami
    • 1
    Email author
  1. 1.Department of Medical Microbiology, Mycology and ImmunologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Laboratory MedicineFukushima Medical University HospitalFukushimaJapan
  3. 3.Japanese Red Cross SocietyKoto-kuJapan
  4. 4.Department of Emergency MedicineTohoku University Graduate School of MedicineSendaiJapan
  5. 5.Department of Cardiovascular MedicineTohoku University Graduate School of MedicineSendaiJapan
  6. 6.Department of PathophysiologyTohoku Pharmaceutical UniversitySendaiJapan
  7. 7.Department of Science of Nursing PracticeTohoku University Graduate School of MedicineSendaiJapan
  8. 8.Research Institute for Biomedical SciencesTokyo University of ScienceNodaJapan

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