title: VAP-1-mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A-induced lymph- and angiogenesis.
abstract: 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 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 lymph- and 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 angiogenesis-related macrophage recruitment. VAP-1 might become a new target for treatment of inflammatory lymph- and angiogenic diseases, including cancer.
authors: Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02115, USA.
authors: Shintaro
authors: S
authors: Nakao
authors: Kousuke
authors: K
authors: Noda
authors: Souska
authors: S
authors: Zandi
authors: Dawei
authors: D
authors: Sun
authors: Mahdi
authors: M
authors: Taher
authors: Alexander
authors: A
authors: Schering
authors: Fang
authors: F
authors: Xie
authors: Yukihiko
authors: Y
authors: Mashima
authors: Ali
authors: A
authors: Hafezi-Moghadam
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D042583:Lymphangiogenesis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse