The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.

The lung lymphatic vasculature is capable of remarkable increases in lymphatic drainage in settings of inflammation and edema; however, the mechanisms driving this are not clear. Here we show that lung injury transforms the configuration of lung lymphatic endothelial cell junctions from a continuous 'zippered' configuration to a discontinuous and permeable 'button' configuration. Despite similarity to the junctional changes often seen in leaky and dysfunctional blood vessels, we find that the shift to button junctions in the lymphatic vasculature has an opposite effect, resulting in augmented lung lymphatic drainage. Mechanistically, we demonstrate that lung lymphatic button junction formation in models of lung injury is dependent on the thrombin receptor protease-activated receptor 1, a known mediator of blood vessel permeability. These results uncover a previously unknown role for the thrombin receptor protease-activated receptor 1 in the lymphatic vasculature that promotes a similar change in junction morphology as seen in blood vessels, but with a disparate effect on lymphatic function.