Development of a mouse model of microscopic polyangiitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14947
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Akita University
• Principal Investigator: Sasaki Takehiko 秋田大学, 医学(系)研究科(研究院), 教授 (50333365)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 血管炎 / リン脂質 / 好中球

Outline of Final Research Achievements

Microscopic polyangiitis (MPA) is a form of small vessel vasculitis (SVV) primarily affecting arterioles, capillaries and venules. Aberrant neutrophil extracellular traps (NETs) play a role in MPA induction but a lack of suitable mouse models has precluded elucidation of the mechanism. We have developed a new mouse model of MPA based on administration of a novel fungal immunostimulant, termed CANDE. CANDE induced NET formation both in vitro and in vivo. CANDE-treated mice displayed disease closely recapitulating human MPA, with anti-neutrophil cytoplasmic autoantibodies (ANCAs) in serum; necrotizing SVV in the lung; and necrotizing glomerulonephritis with crescent formation. Using this MPA model, we demonstrate that loss of phosphoinositide-3-kinase p110g; inhibits NET formation in vitro and in vivo, decreases serum ANCA levels, and alleviates organ damage.

Free Research Field

脂質生物学