title: P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo.
abstract: Selectin-dependent rolling is the earliest observable event in the recruitment of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins. The best-characterized selectin ligand is P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin- dependent rolling in vitro and in vivo. In vitro studies have suggested that PSGL-1 may also be a ligand for E- and L-selectins. To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1-coated microspheres in mouse venules stimulated to express P- and/or E-selectin. Microspheres coated with functional recombinant PSGL-1 rolled in surgically stimulated and tumor necrosis factor alpha (TNFalpha)-stimulated mouse venules. P-selectin deficiency or inhibition abolished microsphere rolling in surgically and TNFalpha-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNFalpha-stimulated venules. The results suggest that P-selectin-PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin-PSGL-1 interaction supports slow rolling.
authors.affiliation: Cardiovascular Research Group and Section of Surgery, Division of Clinical Sciences (NGH), University of Sheffield, United Kingdom. k.norman@sheffield.ac.uk
authors.forename: K E
authors.initials: KE
authors.lastname: Norman
authors.forename: A G
authors.initials: AG
authors.lastname: Katopodis
authors.forename: G
authors.initials: G
authors.lastname: Thoma
authors.forename: F
authors.initials: F
authors.lastname: Kolbinger
authors.forename: A E
authors.initials: AE
authors.lastname: Hicks
authors.forename: M J
authors.initials: MJ
authors.lastname: Cotter
authors.forename: A G
authors.initials: AG
authors.lastname: Pockley
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
mesh_terms: D000818:Animals; D019040:E-Selectin / Q000378:metabolism / Q000494:pharmacology*; D006439:Hemodynamics; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D023421:Models, Animal; D009504:Neutrophils / Q000737:chemistry; D019007:P-Selectin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014699:Venules / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D014409:Tumor Necrosis Factor-alpha