title: P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin under flow. The glycoproteins that enable leukocyte tethering to or rolling on E-selectin are not known. We used gene targeting to prepare PSGL-1-deficient (PSGL-1-/-) mice, which were healthy but had moderately elevated total blood leukocytes. Fluid-phase E-selectin bound to approximately 70% fewer sites on PSGL-1-/- than PSGL-1+/+ neutrophils. Compared with PSGL-1+/+ leukocytes, significantly fewer PSGL-1-/- leukocytes rolled on E-selectin in vitro, because their initial tethering to E-selectin was impaired. The residual cells that tethered rolled with the same shear resistance and velocities as PSGL-1+/+ leukocytes. Compared with PSGL-1+/+ mice, significantly fewer PSGL-1-/- leukocytes rolled on E-selectin in TNF-alpha-treated venules of cremaster muscle in which P-selectin function was blocked by an mAb. The residual PSGL-1-/- leukocytes that tethered rolled with slow velocities equivalent to those of PSGL-1+/+ leukocytes. These results reveal a novel function for PSGL-1 in tethering leukocytes to E-selectin under flow.
authors.affiliation: Warren Medical Research Institute and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Yago
authors.forename: J Michael
authors.initials: JM
authors.lastname: McDaniel
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.forename: Sonia
authors.initials: S
authors.lastname: Pearson-White
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology*; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D019040:E-Selectin; D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D014409:Tumor Necrosis Factor-alpha