title: Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion.
abstract: It has not been determined whether L-selectin-mediated rolling can promote leukocyte adhesion in vivo independent of P- and E-selectin. We used intravital microscopy of E- and P-selectin double-mutant mice (E-/P-) stimulated with tumor necrosis factor-alpha for 6-8 h to investigate the importance of L-selectin-dependent rolling in cremaster muscle venules. Rolling leukocyte flux in E-/P- mice was 9 +/- 2 cells/min compared with 77 +/- 17 cells/min in wild-type (WT) mice. Pretreatment with the L-selectin monoclonal antibody MEL-14 significantly reduced rolling in both E-/P- (by 89%) and WT mice (by 79%). L-selectin-dependent rolling in E-/P- mice resulted in leukocyte adhesion comparable to that seen in WT mice. MEL-14 pretreatment of E-/P- mice reduced leukocyte adhesion by 50%. The majority (approximately 80%) of intravascular leukocytes in both WT and E-/P- mice were neutrophils. We conclude that L-selectin can mediate rolling that results in sufficient leukocyte recruitment to account for the robust inflammatory response seen in E-/P- mice at later times.
authors.affiliation: Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.
authors.forename: U
authors.initials: U
authors.lastname: Jung
authors.forename: C L
authors.initials: CL
authors.lastname: Ramos
authors.forename: D C
authors.initials: DC
authors.lastname: Bullard
authors.forename: K
authors.initials: K
authors.lastname: Ley
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D019040:E-Selectin / Q000502:physiology*; D018390:Gene Targeting; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D019041:L-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D019041:L-Selectin