[HTML][HTML] VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β–but Not VEGF-A–Induced Lymph-and Angiogenesis

S Nakao, K Noda, S Zandi, D Sun, M Taher… - The American Journal of …, 2011 - Elsevier
S Nakao, K Noda, S Zandi, D Sun, M Taher, A Schering, F Xie, Y Mashima…
The American Journal of Pathology, 2011Elsevier
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 …
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.
Elsevier