Cellular and Molecular Life Sciences

, Volume 69, Issue 6, pp 897–914 | Cite as

Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis



The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation, and sprouting. Recent evidence has implied that macrophages act as a direct structural contributor to lymphatic endothelial walls or secret VEGF-C/-D and VEGF-A to initiate lymphangiogenesis in inflamed or tumor tissues. Bone marrow-derived macrophages are versatile cells that express different functional programs in response to exposure to microenvironmental signals, and can be identified by specific expression of a number of proteins, F4/80, CD11b, and CD68. Several causative factors, e.g., NF-κB, IL-1β, TNF-α, SDF-1, M-CSF, especially TonEBP/VEGF-C signaling, may be actively involved in macrophage-induced lymphangiogenesis. Alteration of macrophage phenotype and function has a profound effect on the development and progression of inflammation and malignancy, and macrophage depletion for controlling lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic-associated diseases.


Macrophages Lymphangiogenesis Lymphatic endothelial cells Tumor Inflammation VEGF-A/-C/-D VEGFR-2/-3 



Bone marrow-derived cells


Carcinoembryonic antigen-related cell adhesion molecule-1


Common lymphatic endothelial and vascular endothelial receptor-1


CXC chemokine receptor-4


Extracellular matrix


Endothelial nitric oxide synthase


High-salt diet


Herpes simplex virus-1


Interstitial fluid pressure




Lymphatic endothelial cells




Lymphatic vascular endothelial hyaluronan receptor-1


Macrophage colony-stimulating factor


Matrix metalloproteinase


Macrophage mannose receptor


Mononuclear phagocyte system


Nuclear factor-κB


Prospero-related homeobox-1


Vascular endothelial growth factor-A/-C/-D


Vascular endothelial growth factor receptor-2/-3


Stromal cell-derived factor-1


Tumor-associated macrophages


Transforming growth factor-β


Toll-like receptor-4


Tumor necrosis factor-α


Tonicity-responsive enhancer binding protein


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Human AnatomyOita University Faculty of MedicineOitaJapan

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