THE LYMPHATIC VASCULAR SYSTEM: SECONDARY OR PRIMARY?

Abstract

It has generally been accepted that the blood vascular system is primary and the lymphaticvascular system secondary. Diseases of the blood vascular system are the leading cause formortality and morbidity in developed nations. In contrast, lymphedema is seldom life-threateningand can generally be well-managed by combined physiotherapy. During ontogeny, the bloodvessels and the heart develop much earlier than the lymphatic vessels. However, there is growingevidence that the first vascular system occurring during ontogeny and phylogeny has lymphaticfunctions. Defense mechanisms are crucial for all organisms irrespective of their size.Macrophages precede the emergence of erythrocytes during ontogeny, and their circulation inthe hemolymphatic (more accurately, lymphohematic) system of insects, which do not possesserythrocytes, shows that the lymphatic function is primary whereas the nutritive function issecondary, needed only in larger organisms. In molluscs and arthropods, which have an openvascular system, hemocyanin has both oxygen transporting and defense functions. In vertebrates,the early blood vessels have structural characteristics of lymphatics and express thelymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor-3). Later, flt-4becomes restricted to the definitive lymphatics, which are either formed from the primary vesselsor from mesodermal lymphangioblasts. The primary lymphatic function has become overruled bythe nutritive function in blood vessels of larger animals. The circular movement of cells is drivenby a blood heart, which, however, is not an unique organ. Lymph hearts are present in lowervertebrates, still develop transiently in birds, and are vestigial in the contractile lymphangionwhich “circulates” immune cells. We conclude that the definitive lymphatics are perhapssecondary in mammals, but the blood vascular system seems to develop on the basis of anancestral lymphatic system with lymph hearts.