Netrin-1 suppresses CCL2-driven macrophage migration: implications for modulating vascular inflammation and aortic sinus enlargement in hyperlipidaemic mice
Year: 2026
Type: article
Abstract: Background Atherosclerosis is driven by sustained recruitment and accumulation of monocytes and macrophages within arterial walls through chemokine-mediated pathways. Netrin-1, an immunomodulatory molecule originally identified in neural development, has emerged as a potential regulator of vascular inflammation, though its precise effects on chemokine-driven leukocyte migration remain undefined. Methods We investigated netrin-1 effects on macrophage migration in vitro using real-time impedance-based assays and assessed systemic effects in vivo through intravital microscopy and aortic sinus histology in an inflammation-induced model. Results Netrin-1 selectively inhibited CCL2-driven macrophage migration in vitro , reducing migration when combined with the chemokine compared to chemokine alone. In an acute inflammation mouse model, systemic netrin-1 pre-treatment showed a trend toward the decrease of monocyte adhesion and transmigration into the tissue while increasing rolling interactions, suggesting impaired firm adhesion and diapedesis. Importantly, hyperlipidaemic LDLR − / − mice presented enlarged aortic sinus after being fed a high-fat diet, and this enlargement was not observed when netrin-1 was continuously administered via osmotic minipumps. Conclusions Our data suggests that systemic netrin-1 selectively inhibits chemokine-driven monocyte migration in vitro , with potential implications for reducing vascular inflammatory cell recruitment, an important component of atherogenesis.
Institutions: King's College London, British Heart Foundation
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,020
Funder: British Heart Foundation
OpenAlex ID: W7204892956