Endothelial cells close the gap
Researchers from Sanquin (Amsterdam) and UvA-SILS have revealed that local activity of signalling proteins is required to prevent leakage of blood vessels during the inflammation response. The research was coordinated by Jaap van Buul (Sanquin) and was published in Nature Communications on 27 January 2016.
The wall of blood vessels is lined with specialised cells, known as endothelial cells. These cells form a barrier between blood and the surrounding tissue. White blood cells need to pass through the endothelial cell layer in order to fight inflammation. At the same time, the barrier must stay intact to prevent leakage. Until now, it was unclear how white blood cells can pass through the endothelial cell layer without blood vessel leakage.
To resolve this, advanced fluorescence microscopy techniques were used to visualise the activity of signalling proteins in living endothelial cells during the time that white blood cells pass the cell layer. Jakobus van Unen and Joachim Goedhart (affiliated with the Molecular Cytology group and van Leeuwenhoek Centre for Advanced Microscopy, SILS) contributed to the imaging studies. The resulting movies showed that activity of a signalling protein (RhoGTPase) surrounded the white blood cell. The protein activity leads to local polymerisation of proteins, thereby sealing the gap between the white blood cell and the endothelial cells.
This study has revealed how endothelial cells maintain control over their barrier function when white blood cells pass through this barrier.
The research is funded as part of the FNWI-UvA research priority area systems biology.
Niels Heemskerk, Lilian Schimmel, Chantal Oort, Jos van Rijssel, Taofei Yin, Bin Ma, Jakobus van Unen, Bettina Pitter, Stephan Huveneers, Joachim Goedhart, Yi Wu, Eloi Montanez, Abigail Woodfin & Jaap D. van Buul (2016) F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. NATURE COMMUNICATIONS | 7:10493