ゼブラフィッシュのマクロファージは物理的な創傷シグナルを急速な血管透過性へと変換する
Zaza Gelashvili1,2, Zhouyang Shen1,2,3, Yanan Ma1
1Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Blood vessels near injury sites rapidly dilate, become permeable, and release serum and leukocytes into the wounded tissue to support healing and regeneration. How the vasculature senses distant homeostatic tissue perturbations within seconds-to-minutes remains incompletely understood. Using high-speed imaging of live zebrafish larvae, we monitor two hallmark vascular responses to injury: vessel dilation and serum exudation. By genetic, pharmacologic, and osmotic perturbation along with leukocyte depletion, we show that the cPla2 nuclear membrane mechanotransduction pathway converts a ~ 50 μm/s osmotic wound signal into rapid vessel-permeabilization via perivascular macrophages, 5-lipoxygenase (Alox5a), and leukotriene A4 hydrolase (Lta4h). By revealing a previously undescribed physiological function of nuclear membrane mechanotransduction, we provide real-time insights into the long-range communication of wounds and blood vessels in intact tissue.
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