The human body has two major circulatory systems: the blood and lymphatic vascular systems. Both systems share functional and anatomical similarities and play complementary roles in tissue perfusion and fluid circulation. Nonetheless, the two systems have attracted different levels of scientific and clinical attention. Although the blood vascular system has been extensively studied, in contrast, the lymphatic system has been neglected, despite the essential roles it plays in tissue fluid homeostasis, immune response, and lipid absorption. This is largely due to the lack of lymphatic-specific molecular tools to visualize and characterize lymphatic vessels. However, a number of recent discoveries involving the characterization of lymphatic-specific molecules and lymphatic endothelial cells (ECs) have begun to unravel the mystery of the lymphatic system and have opened a new era of lymphatic research. Moreover, studies of genetic mouse models have provided important insights into the molecular mechanisms underlying lymphatic development, as well as the genetic basis of human diseases associated with the lymphatic system. In this chapter, we review some of the landmark findings that have significantly advanced our current understanding of the lymphatic system.

STRUCTURE AND FUNCTION OF THE LYMPHATIC VASCULAR SYSTEM

The blood vascular system is a closed circular network in which blood leaves and returns to the heart after flowing through the arteries, tissue capillaries, and veins. In comparison, the lymphatic system is a blunt-ended linear system: The initial lymphatic vessels begin at the interstitial spaces of peripheral tissues and organs, and they are connected to the thicker collecting lymphatic vessels, which are eventually connected to the inferior vena cava through the thoracic duct (Figure 169.1, Table 169-1).