Lymphatics in the liver

Abstract

The liver is the largest lymph producing organ. A significant increase in the number of hepatic lymphatic vessels, or lymphangiogenesis, has been reported in various liver diseases, including, but not limited to, cirrhosis, viral hepatitis and hepatocellular carcinoma. Despite its apparent relevance in healthy and diseased livers as these and other observations indicate, the hepatic lymphatic system has been poorly studied. With knowledge of the lymphatic system in other organs and tissues incorporated, this review article addresses the current knowledge of the hepatic lymphatic system and the potential role of lymphatic endothelial cells in the health and the disease of the liver and concludes with a brief description on future directions of the study of the hepatic lymphatic system.

Figure 1. Lymphatic system in the liver.

A majority of lymphatic vessels (specifically, lymphatic capillaries due to lack of smooth muscle cell or pericyte coverage) are located in the portal tract, which accommodates the portal vein, the hepatic artery (HA) and bile ducts. Blood in branches of the portal vein and the hepatic artery flows into the sinusoidal microcirculation (red arrows) where these branches merge and ultimately into the central vein (which coalesces to be the hepatic vein). Sinusoids are covered by fenestrated liver sinusoidal endothelial cells (LSECs). Hepatic lymphatic fluid originates mainly from plasma components filtered through fenestrae of LSECs and flows into the space of Disse, the interstitial space between LSECs and hepatocytes (green arrows). Hepatic stellate cells are also located in this space. Lymphatic fluid in the space of Disse primarily flows through the space of Mall, a space between the stroma of the portal tract and the outermost hepatocytes, into the interstitium of the portal tract and then into lymphatic vessels (green allows). [Upper right box] Hepatic lymphatic endothelium. Vascular endothelial growth factor-C (VEGF-C) is one of the most potent lymphangiogenic factors. Lymphatic endothelial cells (LyECs) express VEGFR3, a receptor for VEGF-C. Hepatic LyECs are also known to express lymphokines, such as C-C-motif chemokine ligand 21 (CCL21) that guides dendritic cells through their expression of C-C chemokine receptor 7 (CCR7). LyECs can take up cholesterols carried by HDL. In normal postnatal liver, it is shown that hematopoietic stem cells can differentiate into LyECs.