Abstract
Expression of the sigma receptor-1 has recently been demonstrated in lymphatic vessels, with a demonstration that its activation by the agonist afobazole leads to lymphatic endothelial production of NO and relaxation of isolated rat lymphatic vessels. 1 Heretofore, this chaperone protein has been shown to be both neuroprotective 2 and cardioprotective, 3 but its function in the lymphatic endothelial has not been elucidated. An examination of its role in lymphatic endothelial barrier integrity was conducted by Motawe et al. and reported in this issue of Lymphatic Research and Biology.
To explore this question, the authors investigated lymphatic endothelial barrier function and glycolytic function in culture human dermal endothelial cells. Transendothelial electrical resistance was utilized as an index of barrier function and the cellular glycolytic rate was determined assessed with the Agilent Seahorse system.
In aggregate, the results reported here suggest that sigma receptor-1 contributes to basal lymphatic endothelial barrier function, potentially through its ability to enhance glycolytic energy production. Of particular interest, the data specifically highlight the therapeutic potential of the receptor's agonists to prevent inflammatory mediation of lymphatic barrier dysfunction. Ideally, one might hope that insight into the function of this receptor–agonist interaction might play a future role in the prevention of the barrier dysfunction that accompanies active lymphatic disease.