VAP-1 - Mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A - Induced lymph- and angiogenesis

Shintaro Nakao, Kousuke Noda, Souska Zandi, Dawei Sun, Mahdi Taher, Alexander Schering, Fang Xie, Yukihiko Mashima, Ali Hafezi-Moghadam

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


Vascular adhesion protein-1 (VAP-1) contributes to inflammatory and angiogenic diseases, including cancer and age-related macular degeneration. It is expressed in blood vessels and contributes to inflammatory leukocyte recruitment. The cytokines IL-1β and vascular endothelial growth factor A (VEGF-A) modulate angiogenesis, lymphangiogenesis, and leukocyte infiltration. The lymphatic endothelium expresses intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, which facilitate leukocyte transmigration into the lymphatic vessels. However, whether lymphatics express VAP-1 and whether they contribute to cytokine-dependent lymph- and angiogenesis are unknown. We investigated the role of VAP-1 in IL-1β- and VEGF-A - induced lymph- and angiogenesis using the established corneal micropocket assay. IL-1β increased VAP-1 expression in the inflamed cornea. Our in vivo molecular imaging revealed significantly higher VAP-1 expression in neovasculature than in the preexisting vessels. VAP-1 was expressed in blood but not lymphatic vessels in vivo. IL-1β - induced M2 macrophage infiltration and lymphand angiogenesis were blocked by VAP-1 inhibition. In contrast, VEGF-A - induced lymph- and angiogenesis were unaffected by VAP-1 inhibition. Our results indicate a key role for VAP-1 in lymph- and angiogenesisrelated macrophage recruitment. VAP-1 might become a new target for treatment of inflammatory lymph- and angiogenic diseases, including cancer.

Original languageEnglish
Pages (from-to)1913-1921
Number of pages9
JournalAmerican Journal of Pathology
Issue number4
Publication statusPublished - Apr 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine


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