White blood cells push their way through barriers to get to infection sites.
New research in the Weizmann Institute of Science has shed light on the subject, especially on the movement of immune cells that race to the sites of infection and inflammation. The study revealed that these cells – white blood cells – actively open large gaps in the internal lining of the blood vessels, so they can exit through the vessel walls and rapidly get to areas of infection.

Prof. Ronen Alon and his group in the Weizmann Institute’s Immunology Department discovered how various white blood cells push their way through the lining of the blood vessels when they reach their particular “exit ramps.” Using their nuclei to exert force, they insert themselves between – as well as into – the cells in the vessel walls called endothelial cells. Dismantling specific filaments within the cytoskeletons – the internal skeletons – of the endothelial cells is what creates the large holes, which are several microns in diameter.

The nucleus is better known as the repository of the cells’ DNA but, as Alon explains, it is also the largest, most rigid structure in the cell. Although it tends to be relatively soft and flexible in white blood cells, the nucleus, when driven by motors specifically engaged for this function, is tough enough to push through the barrier imposed by the blood vessel walls.

To get a complete picture of this crucial activity, the scientists tracked the internal skeletons of endothelial cells as they were crossed by immune cells in real time. They followed the behavior of the nuclei of various white blood cells during active squeezing, as well as the fate of the various types of actin fibers that make up the endothelial cell skeletons. The researchers used a number of methods, including fluorescence and electron microscopy, in collaboration with Dr. Eugenia Klein of the Microscopy Unit; a unique system in Alon’s lab for simulating blood vessels in a test tube; and in vivo imaging with Prof. Sussan Nourshargh of Queen Mary University of London. The results of this research, conducted in Alon’s lab by research students Sagi Barzilai and Francesco Roncato and postdoctoral fellow Dr. Sandeep Kumar Yadav, were recently reported in the journal Cell Reports.