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

Review

Abstract

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.

Keywords

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

Abbreviations

BMDCs

Bone marrow-derived cells

CEACAM-1

Carcinoembryonic antigen-related cell adhesion molecule-1

CLEVER-1

Common lymphatic endothelial and vascular endothelial receptor-1

CXCR-4

CXC chemokine receptor-4

ECM

Extracellular matrix

eNOS

Endothelial nitric oxide synthase

HSD

High-salt diet

HSV-1

Herpes simplex virus-1

IFP

Interstitial fluid pressure

IL-1β

Interleukin-1β

LECs

Lymphatic endothelial cells

LPS

Lipopolysaccharide

LYVE-1

Lymphatic vascular endothelial hyaluronan receptor-1

M-CSF

Macrophage colony-stimulating factor

MMP

Matrix metalloproteinase

MMR

Macrophage mannose receptor

MPS

Mononuclear phagocyte system

NF-κB

Nuclear factor-κB

Prox-1

Prospero-related homeobox-1

VEGF-A/-C/-D

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

VEGFR-2/-3

Vascular endothelial growth factor receptor-2/-3

SDF-1

Stromal cell-derived factor-1

TAMs

Tumor-associated macrophages

TGF-β

Transforming growth factor-β

TLR-4

Toll-like receptor-4

TNF-α

Tumor necrosis factor-α

TonEBP

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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