Lymphatics and blood vessels, lymphangiogenesis and hemangiogenesis: From cell biology to clinical medicine

The past 15 years have witnessed an explosion of knowledge about blood vascular endothelium due in large part to in vitro growth of endothelial cells from both large blood vessels and capillaries. In contrast, little comparable information has accumulated on endothelium of lymphatics, which lie in intimate contact with parenchymal cells and drain excess fluid, macromolecules, particles, and immunocompetent cells in a continuous recirculation between tissues and bloodstream. While structural and functional differences between the two vascular systems have been described in vivo, in tissue sections, and in isolated preparations, similarities are notable in ultrastructure, biochemistry, physiology, and pharmacologic responsiveness, and these may predominate under pathologic conditions. In 1984, three separate groups described in vitro culture of lymphatic endothelial cells from collecting ducts and cavernous lymphangiomas. Lymphatic, like blood vascular, endothelium grows in confluent monolayers, 'sprouts', synthesizes Factor VIII-associated antigen and fibronectin, and ultrastructurally shows Weibel-Palade bodies; overlapping intercellular junctions and anchoring filaments typical of lymphatic endothelium are also found. Genetic, congenital, and acquired disorders such as strangulating fetal nuchal cystic hygromas (Down and Turner syndromes), vascular tumors and dysmorphogenesis (Maffucci and Klippel-Trenaunay syndromes), Kaposi's sarcoma, lymphogenous and hematogenous spread of cancer, and parasitic infestations such as filariasis, share overlapping abnormalities in formation, growth, and/or neoplasia of lymphatics and blood vessels. In these and similar clinical disorders, confusion often exists as to the nature of the cell or tissue of origin, and insight into the role and control of hemangiogenesis and lymphangiogenesis is still in its infancy. Nonetheless, with the ever widening array of investigative techniques, it is not only timely but imperative to explore the endothelial biology underlying these inborn and acquired disorders.