Zebrafish macrophages convert physical wound signals into rapid vascular permeabilization

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 cPla 2 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.