Study on pathogenesis of disorders caused by neutrophil dysfunction using novel analytical techniques and development of an innovative strategy to control neutrophils
| Project/Area Number |
25670472
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MORIO Tomohiro 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30239628)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 好中球 / 活性酸素産生 / プライミング / MAL / 敗血症 / 膜透過性タンパク / 免疫学 / 遺伝子 / 感染症 / 細胞・組織 |
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| Outline of Final Research Achievements |
We observed activation of PI3K (class IA, IB) in neutrophils upon signal through Fcgamma receptor. Stimulation with LPS or SAA-1 for neutrophils pre-cultured in the presence of G-CSF, which resembled locally infiltrating long-lived neutrophils, resulted in decrease of IL-4 production in LPS stimulation and increased IL-4 production in SAA-1 administration. We generated CPP-MAL, membrane-targeting type of CPP-MAL, and intracellular retention type of CPP-MAL, transduced them into human neutrophils, and found priming effect when transduced with the membrane-targeting type.
Neutrophils from patients with sepsis exhibited lower ROS production at day 3 compared to that at day 0; and neutrophils from severe sepsis showed lower CXCR2 and PILR alpha expression. Several cellular substrates were tyrosine-phosphorylated in the neutrophils. We also optimized the method to differentiate iPS cell into mature neutrophils in this study.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies2014
Author(s)
Marciano BE, Huang CY, Joshi G, Rezaei N, Carvalho BC, Allwood Z, Ikinciogullari A, Reda SM, Gennery A, Thon V, Espinosa-Rosales F and et al
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Journal Title
J Allergy Clin Immunol.
Volume: 133(4)
Pages: 1134-41
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Case of Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome Accompanied by Nephrosclerosis, Splenomegaly and Intestinal Lesions.2013
Author(s)
Yamamoto A, Morio T, Kumaki E, Yamazaki H, Iwai H, Kubota T, Miyasaka N, Kohsaka H.
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Journal Title
J Genet Syndr Gene Ther.
Volume: 4
Related Report
Peer Reviewed
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[Journal Article] Am80, a retinoic acid receptor agonist, ameliorates murine vasculitis through the suppression of neutrophil migration and activation2013
Author(s)
Miyabe C, Miyabe Y, Miura NN, Takahashi K, Terashima Y, Toda E, Honda F, Morio T, Yamagata N, Ohno N, Shudo K, Suzuki J, Isobe M, Matsushima K, Tsuboi R, Miyasaka N, Nanki T
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Journal Title
Arthritis Rheum
Volume: 65
Issue: 2
Pages: 503-512
DOI
Related Report
Peer Reviewed
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