Genesis and pathogenesis of lymphatic vessels

Abstract

The lymphatic system is generally regarded as supplementary to the blood vascular system, in that it transports interstitial fluid, macromolecules, and immune cells back into the blood. However, in insects, the open hemolymphatic (or lymphohematic) system ensures the circulation of immune cells and interstitial fluid through the body. The Drosophila homolog of the mammalian vascular endothelial growth factor receptor (VEGFR) gene family is expressed in hemocytes, suggesting a close relationship to the endothelium that develops later in phylogeny. Lymph hearts are typical organs for the propulsion of lymph in lower vertebrates and are still transiently present in birds. The lymphatic endothelial marker VEGFR-3 is transiently expressed in embryonic blood vessels and is crucial for their development. We therefore regard the question of whether the blood vascular system or the lymphatic system is primary or secondary as open. Future molecular comparisons should be performed without any bias based on the current prevalence of the blood vascular system over the lymphatic system. Here, we give an overview of the structure, function, and development of the lymphatics, with special emphasis on the recently discovered lymphangiogenic growth factors.

Similarities and differences of human and experimental mouse lymphangiomas

“…Deletion of VEGF-D in mice does not have any obvious effects (Baldwin et al, 2005), whereas transgenic over-expression of VEGF-D in the skin of mice induces lymphangiogenesis after birth (Karpanen et al, 2006). Human VEGF-D applied on the chorioallantoic membrane of birds induces both lymphangiogenesis and hemangiogenesis (Jeltsch et al, 2003). Effects in the human remain to be studied.…”

Lymphangiogenic Growth Factor Responsiveness Is Modulated by Postnatal Lymphatic Vessel Maturation

“…The lymphatic endothelial cells lack tight interendothelial junctions and are attached to the surrounding extracellular matrix by anchoring filaments, while valves serve to prevent lymph backflow in the absence of a strong propulsive pressure. 2 Defects of lymphatic vessel function can lead to lymphedema, a condition characterized by swelling of extremities due to fluid accumulation in tissues. 3 Lymphatic vessels also represent the primary route of metastatic spread for many types of human cancers, 4 and they are furthermore involved in the regulation of inflammatory responses in various pathological conditions.…”

Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3

“…Anecdotal cases of in utero hydrothorax and nonimmune hydrops fetalis have been reported in individuals with HL-I and other primary lymphedema syndromes (Jernite et al 1992;Lev-Sagie et al 2003;Fang et al 2000;Irrthum et al 2003). VEGFR3 is known to have a major role in lymphangiogenesis, mainly of the superficial lymphatic channels (Jeltsch et al 2003). Our report indicates that VEGFR3 may have a lesser yet nonnegligible role in the development of major lymphatic ducts, such as the thoracic duct.…”