title: Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation.
abstract: Selectin adhesion molecules mediate leukocyte rolling on activated endothelium, a prerequisite to leukocyte accumulation at sites of inflammation. The precise role of each selectin (E-, P-, and L-) in this process is unclear and may vary depending on the particular inflammatory stimulus, vascular bed, leukocyte subset, and species; most data suggest discrete functional roles for each selectin. To define the relative roles of E- and P-selectin in mediating neutrophil accumulation in acute dermal inflammation, mice genetically deficient in E-selectin, P-selectin, or both E- and P-selectin were injected intradermally with zymosan. Luminal endothelial expression of E- and P-selectin in response to zymosan was documented in wild-type mice by intravenous administration of fluorochrome-labeled anti-E- and anti-P-selectin antibodies. In mice deficient in E- or P-selectin, neutrophil accumulation was unchanged or only subtly reduced relative to wild-type control mice. In mice deficient in both E- and P-selectin, neutrophil accumulation was significantly reduced (87% at 4 hours and 79% at 8 hours). These data demonstrate that, in this model of acute inflammation, there is considerable overlap in the functions of E- and P-selectin; loss of both selectins was required to impair neutrophil accumulation.
authors.affiliation: Departments of Pathology and Internal Medicine and the Howard Hughes Medical Institute at The University of Michigan Medical Center, Ann Arbor, MI 48109-0680, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Homeister
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: P S
authors.initials: PS
authors.lastname: Frenette
authors.forename: R O
authors.initials: RO
authors.lastname: Hynes
authors.forename: D D
authors.initials: DD
authors.lastname: Wagner
authors.forename: J B
authors.initials: JB
authors.lastname: Lowe
authors.forename: R M
authors.initials: RM
authors.lastname: Marks
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D015054:Zymosan / Q000633:toxicity
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D015054:Zymosan; D009195:Peroxidase