Leakage from blood and lymphatic vessels is differently regulated

2020-09-09

Researchers from IGP show in a new study that cell signalling regulating vessel leakage differs between blood and lymphatic vessels. The findings suggest a possibility to modulate this signalling in order to selectively control lymphatic vessel function and to treat diseases characterised by lymphatic vessel leakage.

Blood and lymphatic vessels both transport fluids, cells and different substances in the body. Tthe inner wall of both vessel types is lined with a type of cells called endothelial cells. To prevent leakage the endothelial cells are tightly linked to each other but there are vessels that should release fluid or cells and to allow this the links between the cells must be reduced.

Neighbouring endothelial cells are interconnected via cell-cell junctions formed of specialised proteins. In the present study the researchers have examined whether the proteins EphrinB2 and EphB4 have a similar role in regulating the cell-cell junctions, and thereby vessel function, in blood and lymphatic vessels.

“The signalling protein EphrinB2 and its receptor EphB4 have important functions during embryonic blood and lymphatic vessel development, but they are also present in adult endothelial cells. We studied genetic mouse models that lacked EphB4 or EphrinB2 and saw that this resulted in disrupted endothelial junctions in lymphatic vessel but not in blood vessels,” says Taija Mäkinen, professor at IGP, who has led the study.

The researchers continued to study the mechanism by which EphB4 and EphrinB2 selectively regulate lymphatic endothelial junctions. They found that loss of EphB4-EphrinB2 signalling led to a reduction of the protein CLDN5, which is part of the cell-cell junctions. In addition, the actin cytoskeleton, a network of fibrillar proteins inside the cells that is connected to the junctional proteins, was also affected.

“We have uncovered that in lymphatic vessels the EphB4-EphrinB2 signalling pathway has to be constantly activated at a basal level to regulate the actin cytoskeleton and thereby maintain the integrity of endothelial cell junctions. This suggests different mechanisms for maintaining junction stability in blood and lymphatic vessels. We think that therapeutic modulation of EphrinB2-EphB4 signalling could be tested as a strategy to treat bacterial infections or other human diseases where lymphatic vessel permeability is increased,” says Taija Mäkinen.

The study has been published in the journal eLife and was performed in collaboration with researchers in Gothenburg, UK, Finland, Germany and Spain.

Mer information:
Paper in eLife
Taija Mäkinen’s research