Immune Cell Trafficking in the Lymphatics, Hyaluronan Biology and Tumour Metastasis

As an integral part of the immune system, the lymphatics enable immune surveillance by shepherding the migration of antigen-laden immune cells to draining lymph nodes (dLNs), as well as handling the clearance of macrophages and neutrophils from sites of injury and infection. In addition, the lymphatics play key roles as conduits for tumour metastasis. The molecular mechanisms controlling entry to the lymphatics in these different contexts have yet to be fully elucidated. However, it is clear that in most cases they involve coordination between the processes of chemotaxis and cell adhesion within the specialized endothelial junctions of initial lymphatic capillaries for transit to the vessel lumen. A fundamental mediator of such adhesion is the large matrix glycosaminoglycan hyaluronan, and growing evidence indicates anchorage of hyaluronan to the surface of migrating cells and appropriate engagement with LYVE-1, its’ primary receptor in lymphatic endothelium are critical to the entry process. The present chapter outlines the main properties of hyaluronan and how they support the trafficking of leucocytes for immunity and inflammation. In addition, it discusses the evidence that hyaluronan may also aid the invasion and systemic dissemination of metastasizing tumour cells.