# Zebrafish macrophages convert physical wound signals into rapid vascular permeabilization

## TL;DR

Zebrafish macrophages detect fast wound signals and quickly make nearby blood vessels leaky to aid healing.

## Contribution

Discovers a new role for nuclear membrane mechanotransduction in wound-induced vascular permeability.

## Key findings

- Macrophages use cPla2 to convert osmotic wound signals into vascular permeabilization.
- The pathway involves Alox5a and Lta4h in perivascular macrophages.
- This process occurs within seconds to minutes after injury.

## 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.

Real-time imaging in zebrafish shows that macrophages convert fast osmotic wound signals into rapid vessel permeabilization via cPla2-dependent nuclear membrane mechanotransduction.