Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish.

Tissue-resident macrophages populate nearly all organs, where they adopt tissue-specific roles essential for immune defense, tissue development and homeostasis. Their dysfunction contributes to inflammation, cancer and other diseases. Whether a dedicated macrophage population operates within the extensive vascular network, one of the body's largest and most widely distributed tissues, has remained unknown. Here, using high-resolution spatiotemporal live imaging in zebrafish embryos, we identify a distinct population of macrophages residing within blood vessels, termed blood vessel-resident macrophages (bMΦs), with conserved features in mice. bMΦs patrol the bloodstream, clear foreign particles and unfit cells, and act as first responders to endothelial damage. bMΦs emerge directly from axial vessels through an atypical endothelial-to-macrophage transition that is independent of Runx1 and Csf1r. Our findings reveal a previously unrecognized macrophage population dedicated to vascular immune surveillance, uncovering mechanisms that preserve blood and vessel integrity and offering potential therapeutic avenues for bloodborne and vascular diseases.