Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion.
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.
Jung
U
U
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.
Ramos
C L
CL
Bullard
D C
DC
Ley
K
K
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*
D019040:E-Selectin; D019007:P-Selectin; D019041:L-Selectin