UC San Diego

Inflammation has a profound effect on the vascular circulation, but little is known about its effect on the lymphatics. In the first half of this dissertation, I examine the effect of inflammation directly on the barrier properties of the initial lymphatics in the rat spinotrapezius muscle. I hypothesize that fluid that travels from the interstitium into the initial lymphatics must travel through the primary valves, a unidirectional valve system that allows fluid to flow into the lymphatics, but not back out. I determine that a particle with diameter 0.5 [mu]m is able to pass through the primary valves, but particles with diameter 0.8 [mu]m and larger are unable to. Acute inflammation does not change this property, although it does allow fluid to escape back into the interstitium at a rate greater than that in healthy animals. This suggests that during inflammation the initial lymphatics are compromised and the primary valves do not function as a unidirectional valve system. In addition, I hypothesize that the lymphatic system is responsible for removing toxic peptides and lipids from the interstitium to limit their damage to the tissue. By doing this, the lymphatic endothelium, lymphocytes and dendritic cells collected by the lymphatics, and cells in the lymph node are being exposed to these toxic mediators. I provide evidence that lymph collected from the rat mesenteric lymph duct is toxic both under healthy conditions as well as under inflammatory conditions