Dichotomous effects of in vivo and in vitro ionizing radiation exposure on lymphatic function.

On the one hand, lymphatic dysfunction induces interstitial edema and inflammation. On the other hand, the formation of edema and inflammation induce lymphatic dysfunction. However, informed by the earlier reports of undetected apoptosis of irradiated lymphatic endothelial cells (LECs) in vivo, lymphatic vessels are commonly considered inconsequential to ionizing radiation (IR)-induced inflammatory injury to normal tissues. Due primarily to the lack of understanding of the acute effects of IR exposure on lymphatic function, acute edema and inflammation-common sequelae of IR exposure-have been ascribed solely to blood vessel damage. Therefore, in the present study, the lymphatic acute responses to IR exposure were quantified to evaluate the hypothesis that IR exposure impairs lymphatic pumping. Rat mesenteric lymphatic vessels were irradiated in vivo or in vitro, and changes in pumping were quantified in isolated vessels in vitro. Compared to sham-treated vessels, pumping was lowered in lymphatic vessels irradiated in vivo but increased in vessels irradiated in vitro. Furthermore, unlike in blood vessels, the acute effects of IR exposure in lymphatic vessels were not mediated by nitric oxide-dependent pathways in either in vivo or in vitro irradiated vessels. After cyclooxygenase blockade, pumping was partially restored in lymphatic vessels irradiated in vitro but not in vessels irradiated in vivo. Taken together, these findings demonstrated that lymphatic vessels are radiosensitive, and LEC apoptosis alone may not account for all the effects of IR exposure on the lymphatic system.