Development of the lymphatic vascular system: A mystery unravels

Abstract

The blood vascular and the lymphatic system play complementary roles in tissue perfusion and fluid reabsorption. Despite its critical role in mediating tissue fluid homeostasis, intestinal lipid absorption, and the immune response, the lymphatic system has not received as much attention as the blood vascular system, largely due to a lack of lymphatic-specific markers and to the dearth of knowledge about the molecular regulation of lymphatic development and function. A series of recent landmark studies now significantly has advanced our understanding of the lymphatic system. Based upon the discovery and characterization of lymphatic-specific growth factors, receptors, and transcriptional regulators, the mystery of lymphatic vascular system development begins to be unraveled. The successful isolation and cultivation of blood vascular and lymphatic endothelial cells has enabled comparative molecular and cellular analyses of these two genetically and developmentally closely related cell lineages. Moreover, studies of several genetic mouse models have set the framework for a new molecular model of embryonic lymphatic vascular development and have identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Although these rapid advances already have led to development of the first lymphatic-targeted molecular therapies, there still remain many unanswered questions regarding almost every aspect of lymphatic vascular biology, making the lymphatic system a highly exciting and rewarding field of study.

Profound but Dysfunctional Lymphangiogenesis via Vascular Endothelial Growth Factor Ligands from CD11b+ Macrophages in Advanced Ovarian Cancer

“…Furthermore, LECs express low levels of VEGFR-2 that are enhanced during embryonic development, wound healing, and tumor progression. Thus, lymphangiogenesis is not entirely dependent on VEGFR-3 in certain conditions (21,25). Indeed, our coimmunostaining analyses revealed that, in OVCA-induced lymphangiogenesis, the LECs strongly expressed both VEGFR-2 and VEGFR-3 (Fig.…”

“…[21][22][23][24][25]. Moreover, proinflammatory cytokineinduced activation of macrophages may be involved in pathologic lymphangiogenesis by reciprocal interactions with the VEGF-C/D-VEGFR-3 system (26)(27)(28)(29)(30).…”

Synchrony of High Endothelial Venules and Lymphatic Vessels Revealed by Immunization

“…HEVs also display CCL19 and CCL21, which are instrumental in encouraging the entrance of naive T cells and directing dendritic cell (DC) traffic in the LN. Lymphatic vessels, distinguished by LYVE-1 (8), play important roles in fluid regulation and immune responses. Afferent LVs allow entrance of soluble Ag and APCs into LNs and efferent LVs return lymphocytes back to the blood circulation.…”

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

“…Although the lymphatic system was first described by the Italian anatomist Asellius in 1627, as vein-like vessels carrying whitish fluid, research in this area has progressed slowly compared with that in blood vessels [1]. One of the major limitations has been the lack of histological, ultrastructural, and immunohistochemical markers that can accurately differentiate blood endothelial cells (BECs) from lymphatic endothelial cells (LECs).…”