Lymphatic endothelial cells, or LECs, are the specialized cells forming the inner lining of lymphatic vessels. These vessels are part of the lymphatic system, a network involved in managing tissue fluid, absorbing dietary fats, and participating in immune defense. LECs are the fundamental building blocks of this network, creating the structure for these processes.
Unique Characteristics of Lymphatic Endothelial Cells
Lymphatic endothelial cells possess distinct features that separate them from their counterparts in blood vessels, known as blood endothelial cells (BECs). Morphologically, LECs are flatter and wider, with an “oak leaf” shape. This structure allows them to overlap, creating specialized intercellular junctions. Unlike the tight, zipper-like junctions of most blood vessels, the initial lymphatic capillaries have discontinuous, button-like junctions that act as primary valves.
These unique junctions are tethered to the surrounding tissue by anchoring filaments. When fluid pressure builds in the interstitial space—the area between cells—it pulls on these filaments. This action opens the flaps between LECs, allowing fluid, macromolecules, and even cells to enter the lymphatic vessel. This mechanism is a direct result of their specific structural design.
Further distinguishing LECs is their molecular signature. Scientists use specific protein markers to identify them, such as the transcription factor Prox1, a master regulator for LEC development. Other markers include LYVE-1 and podoplanin (PDPN). These markers are not typically found on BECs, providing a reliable way to differentiate the two cell types. The basement membrane of initial lymphatics is also characteristically thin or absent, unlike the more robust basement membrane supporting blood capillaries.
Essential Functions in Health
The structure of lymphatic endothelial cells enables their functions in maintaining a healthy state. One of their primary roles is maintaining interstitial fluid homeostasis. LECs absorb excess fluid, proteins, and other large molecules that leak from blood capillaries into the tissues. By forming lymph, they prevent the fluid buildup that leads to swelling, or edema.
LECs are also integral to immune surveillance and trafficking. They act as gatekeepers, facilitating the entry of immune cells like dendritic cells and T cells from the tissues into lymphatic vessels. These cells are then transported to lymph nodes, where they can present antigens and initiate adaptive immune responses. LECs express specific signaling molecules and adhesion molecules on their surface that guide these immune cells into the lymphatic network.
A specialized function of LECs is seen in the small intestine. Here, lymphatic capillaries called lacteals are responsible for absorbing dietary fats and fat-soluble vitamins. These fat molecules are packaged into large particles called chylomicrons, which are too big to enter the blood capillaries directly. The unique permeability of the LECs lining the lacteals allows for the efficient uptake of these fats into the lymphatic system, from which they are eventually delivered into the bloodstream.
Involvement in Disease Processes
When lymphatic endothelial cells are damaged or function incorrectly, it can contribute to a range of diseases. Lymphedema is a primary example, characterized by chronic swelling due to the accumulation of interstitial fluid. This condition can be primary, resulting from genetic mutations that affect LEC development or function, or secondary, caused by damage to lymphatic vessels from surgery, radiation therapy for cancer, or infections.
LECs also play a part in the spread of cancer. Many tumors induce the growth of new lymphatic vessels, a process called lymphangiogenesis, by releasing specific growth factors like VEGF-C and VEGF-D. These new vessels provide an escape route for cancer cells, allowing them to metastasize to regional lymph nodes and then to distant organs. Blocking lymphangiogenesis is a potential therapeutic strategy.
Beyond lymphedema and cancer, LECs are involved in inflammatory and immune disorders. During inflammation, they help resolve the issue by draining inflammatory fluids, cells, and mediators from the affected tissue. However, in chronic inflammatory conditions or autoimmune diseases, their signaling and interactions with immune cells can sometimes perpetuate the disease state. Lymphatic malformations, which are congenital abnormalities of lymphatic vessels, are another condition directly linked to the abnormal growth and organization of LECs.
Investigating Lymphatic Endothelial Cells
Scientists use various methods to study lymphatic endothelial cells. In vitro studies involve isolating and culturing LECs in a laboratory setting. These cell culture models allow for controlled experiments to investigate cellular processes, such as how LECs respond to growth factors or form vessel-like tubes. Bioengineered “lymphatic-vessel-on-a-chip” models create three-dimensional microfluidic environments that more closely mimic the conditions inside the body for detailed studies of barrier function.
In vivo studies often utilize genetically engineered mouse models. For instance, mice can be engineered so that their LECs produce a fluorescent protein, allowing researchers to visualize the lymphatic network in living animals using techniques like intravital microscopy. This provides real-time insights into processes like immune cell trafficking or lymph flow. The molecular markers that distinguish LECs are used for identifying and tracking these cells in tissue samples.
This research is important for advancing knowledge of biological processes. Investigating their role in disease helps uncover the mechanisms behind conditions like cancer metastasis and lymphedema. This knowledge is used to identify potential therapeutic targets, with the goal of developing novel treatments, such as promoting lymphatic growth in lymphedema or inhibiting it to prevent cancer spread.