| 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 |
|---|
| 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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