The mechanisms by which immune cells pass through the endothelial barrier of blood vessel walls to fight against pathogens and other threats have been elusive. New research now indicates that leukocytes use their nuclei to form lobes that enable them to cross endothelial cells. The force created by the lobes causes the rapid disassembly of thin actin filaments that form part of the endothelial cytoskeleton.
In their Cell Reportsstudy, researchers at The Weizmann Institute of Science in Israel and their colleagues tracked how 3 different types of leukocytes (neutrophils and 2 types of T cells) squeeze through the endothelial cytoskeleton. Fluorescence imaging, electron microscopy, and ultrastructural analysis revealed that nuclear squeezing of the different leukocytes occurred without rupture of the endothelial stress fibers, which mediate cell contraction. Instead, the endothelial gaps and pores generated by transmigrating leukocytes involved disassembly of the small interlacing actin filaments that are woven throughout these thicker elastic fibers within individual endothelial cells. Blocking endothelial actin turnover abolished leukocyte nuclear squeezing, whereas increasing actin filament density did not.
Hampton T. New Insights on How Immune Cells Breach Blood Vessel Walls. JAMA. 2017;317(9):899. doi:10.1001/jama.2017.1067