TY - JOUR
T1 - VAP-1 - Mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A - Induced lymph- and angiogenesis
AU - Nakao, Shintaro
AU - Noda, Kousuke
AU - Zandi, Souska
AU - Sun, Dawei
AU - Taher, Mahdi
AU - Schering, Alexander
AU - Xie, Fang
AU - Mashima, Yukihiko
AU - Hafezi-Moghadam, Ali
N1 - Funding Information:
Supported by National Institutes of Health grant AI050775 , the Malaysian Palm Oil Board , American Health Assistance Foundation , an overseas Research Fellowship Award from Bausch & Lomb , a Fellowship Award from the Japan Eye Bank Association , and Tear Film & Ocular Surface Society Young Investigator Fellowship (to S.N. under the mentorship of A.H.-M.).
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2011.01.011
DO - 10.1016/j.ajpath.2011.01.011
M3 - Article
C2 - 21435467
AN - SCOPUS:79953655835
SN - 0002-9440
VL - 178
SP - 1913
EP - 1921
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -
