| First Author | Nakao S | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 4 | Pages | 1913-21 |
| PubMed ID | 21435467 | Mgi Jnum | J:169843 |
| Mgi Id | MGI:4943346 | Doi | 10.1016/j.ajpath.2011.01.011 |
| Citation | Nakao S, et al. (2011) VAP-1-Mediated M2 Macrophage Infiltration Underlies IL-1beta- but Not VEGF-A-Induced Lymph- and Angiogenesis. Am J Pathol 178(4):1913-21 |
| abstractText | 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-1beta 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-1beta- and VEGF-A-induced lymph- and angiogenesis using the established corneal micropocket assay. IL-1beta 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-1beta-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. |
