Lymphatic endothelial cells, inflammatory lymphangiogenesis, and prospective players.

De novo lymphangiogenesis influences different pathological courses via modulating tissue fluid homeostasis, macromolecule absorption, and leukocyte transmigration. During the past decade, improved understanding of lymphatic biology, especially VEGF-C/-D/VEGFR-3-mediating lymphangiogenesis has substantially promoted clinical research in lymphatic insufficiency. The role of lymphangiogenesis in the setting of the inflammatory processes observed in transplants, inflamed cornea, wound healing, acquired lymphedema and tumor invasion, however, remains to be elucidated. The chemokine family of peptide chemoattractants and other mediators, e.g., CCL21-CCR7, D6, NF-kappaB and TNF-alpha may be important contributors to pathophysiological changes of lymphatic endothelial cells (LECs) and inflammatory lymphangiogenesis. Dendritic cells and macrophages may also involve in LEC proliferation and differentiation. Increased knowledge of LEC-specific modulators in inflammatory microenvironment is vital for prevention and treatment of lymphatic-associated diseases.