Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

• DOI: 10.7554/elife.66074
• Publication Date: 2021-08-25T12:00:30Z
• Authors: Janine JG Arts; Eike K Mahlandt; Max LB Grönloh; Lilian Schimmel; Ivar Noordstra; Emma Gordon; Abraham CI van Steen; Simon Tol; Barbara Walzog; Jos van Rijssel; Martijn A Nolte; Marten Postma; Satya Khuon; John M Heddleston; Eric Wait; Teng Leong Chew; Mark Winter; Eloi Montanez; Joachim Goedhart; Jaap D van Buul
• Keywords: Male; 0301 basic medicine; endothelium; QH301-705.5; Neutrophils; Science; Immunology; Green Fluorescent Proteins; 610; Mice, Transgenic; Endoteli; Cell Line; Mice; 03 medical and health sciences; Microscopy, Electron, Transmission; 616; Human Umbilical Vein Endothelial Cells; Animals; Humans; Immunologia; Endothelium; Biology (General); Leucocytes; Muscle, Skeletal; GTPase; Inflammation; Leucòcits; Q; R; Cell Biology; protrusions; Inflamació; Intercellular Junctions; Gene Expression Regulation; inflammation; Transmigration; Medicine; actin

Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter inflamed tissue. Evidence accumulates that use preferred exit sites, alhough it is not yet clear how these hotspots in are defined and they recognized by leukocyte. Using lattice light sheet microscopy, we discovered prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, junctional present an asymmetric manner, meaning one shows protrusion adjacent does not. Consequently, cross junction migrating underneath protruding cell. These depend on Rac1 activity using a photo-activatable probe, could artificially generate local exit-sites leukocytes. Overall, have new mechanism uses induced facilitate/steer leukocyte escape/exit from vessel walls.