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1 Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia 22908; and 2 Department of Comparative Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294
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-
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
(~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.
inflammation; leukocyte adhesion; knockout mice; intravital microscopy
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