Lymphatic biology and the microcirculation: past, present and future.

Because of the role that lymphatics have in fluid and macromolecular exchange, lymphatic function has been tightly tied to the study of the microcirculation for decades. Despite this, our understanding of many basic tenets of lymphatic function is far behind that of the blood vascular system. This is in part due to the difficulty inherent in working in small, thin-walled, clear lymphatic vessels and the relative lack of lymphatic specific molecular/cellular markers. The application of cellular and molecular tools to the field of lymphatic biology has recently produced some significant developments in lymphatic endothelial cell biology. These have propelled our understanding of lymphangiogenesis and related fields forward. Whereas the use of some of these techniques in lymphatic muscle biology has somewhat lagged behind those in the endothelium, recent developments in lymphatic muscle contractile and electrical physiology have also led to advances in our understanding of lymphatic transport function, particularly in the regulation of the intrinsic lymph pump. However, much work remains to be done. This paper reviews significant developments in lymphatic biology and discusses areas where further development of lymphatic biology via classical, cellular, and molecular approaches is needed to significantly advance our understanding of lymphatic physiology.