Nitric oxide (NO) side of lymphatic flow and immune surveillance

The loss of cancer or bacteria detection by the immune system is traditionally looked at from the point of cell–cell or humoral mediator–cell interactions. However, immune surveillance in lymphatics critically requires cell transport along the lymphatics for entry of antigen/dendritic cells into the draining lymph node (1). Reductions in collecting lymphatic function affect all subsequent immune response. The work by Liao et al. (2), from a team well-versed in the complexities and limitations of transport in tumors, brings to light that lymphatic transport can be limited by a mechanism that is controlled by nitric oxide (NO) derived from bone marrow myeloid cells. The study is focused on the smooth muscle-equipped contractile (also denoted collecting) lymphatics in a part of the lymphatics located proximal to the initial lymphatics (2). Initial lymphatics, rich in numbers and deeply embedded in tissue parenchyma, consist of pure endothelial channels without perivascular cells (e.g., pericytes) and smooth muscle cells. They have overlapping cell junctions forming primary valves in addition to traditional secondary lymph valves, and they rely on surrounding tissue motions to achieve periodic lymph channel expansion and compression for collection of interstitial fluid and fluid transport inside the lymphatics (3). By contrast, the contractile lymphatics are equipped with rows of bileaflet valves and contract …