Portal de Periódicos da CAPES

Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D

2013; Elsevier BV; Volume: 122; Issue: 22 Linguagem: Inglês

10.1182/blood-2012-11-466532

1528-0020

Kar Wai Tan, Shu Zhen Chong, Fiona H. S. Wong, Maximilien Evrard, Sandra Min-Li Tan, Jo Keeble, D.M. Kemeny, Lai Guan Ng, Jean‐Pierre Abastado, Véronique Angeli,

Sympathectomy and Hyperhidrosis Treatments

Abstract Lymphangiogenesis is an important physiological response to inflammatory insult, acting to limit inflammation. Macrophages, dendritic cells, and lymphocytes are known to drive lymphangiogenesis. In this study, we show that neutrophils recruited to sites of inflammation can also coordinate lymphangiogenesis. In the absence of B cells, intranodal lymphangiogenesis induced during prolonged inflammation as a consequence of immunization is dependent on the accumulation of neutrophils. When neutrophils are depleted in wild-type mice developing skin inflammation in response to immunization or contact hypersensitization, lymphangiogenesis is decreased and local inflammation is increased. We demonstrate that neutrophils contribute to lymphangiogenesis primarily by modulating vascular endothelial growth factor (VEGF)-A bioavailability and bioactivity and, to a lesser extent, secreting VEGF-D. We further show that neutrophils increased VEGF-A bioavailability and bioactivity via the secretion of matrix metalloproteinases 9 and heparanase. Together, these findings uncover a novel function for neutrophils as organizers of lymphangiogenesis during inflammation.