title: 'Slings' enable neutrophil rolling at high shear.
abstract: Most leukocytes can roll along the walls of venules at low shear stress (1 dyn cm−2), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here we show that these long tethers do not retract as postulated, but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.
authors: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors: Prithu
authors: P
authors: Sundd
authors: Edgar
authors: E
authors: Gutierrez
authors: Ekaterina K
authors: EK
authors: Koltsova
authors: Yoshihiro
authors: Y
authors: Kuwano
authors: Satoru
authors: S
authors: Fukuda
authors: Maria K
authors: MK
authors: Pospieszalska
authors: Alex
authors: A
authors: Groisman
authors: Klaus
authors: K
authors: Ley
mesh_terms: D000268:Adhesiveness; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036904:Leukocyte Rolling; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D033081:Shear Strength; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014699:Venules / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C480027:ICAM-2 protein, mouse; C090509:Icam1 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D018799:Intercellular Adhesion Molecule-1