Study on pathogenesis of disorders caused by neutrophil dysfunction using novel analytical techniques and development of an innovative strategy to control neutrophils

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670472
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MORIO Tomohiro 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30239628)
• Project Period (FY): 2013-04-01 – 2015-03-31
• 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

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.

Free Research Field

小児科学、免疫学