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*
Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; and
Department of Immunology, Duke University Medical Center, Durham, NC 27710
Although L-selectin mediates lymphocyte attachment to endothelial
venules of peripheral lymph nodes, its role in leukocyte recruitment
into tissues following Ag challenge is less well established. The
objective of this study was to systematically examine the role of
L-selectin in leukocyte rolling in the peripheral microvasculature
during the first 24 h of an immune response. A type I
hypersensitivity response was elicited in wild-type (C57BL/6) and
L-selectin-deficient mice by systemic (i.p.) sensitization and
intrascrotal challenge with chicken egg OVA. The cremaster
microcirculation was observed in untreated and sensitized mice 4, 8,
and 24 h post-Ag challenge by intravital microscopy. Leukocyte
recruitment in L-selectin-deficient mice and wild-type mice treated
with an L-selectin function-blocking mAb was examined at each time
point. Ag challenge induced a significant increase in leukocyte rolling
(60 cells/min/venule to
300 cells/min/venule) in wild-type mice at
424 h. This response was reduced by approximately 6070% in
L-selectin-deficient mice and in wild-type mice treated with an
L-selectin-blocking mAb. P-selectin blockade by Ab completely inhibited
leukocyte rolling at 424 h in wild-type animals and also blocked the
residual rolling seen in L-selectin-deficient mice. Blocking E-selectin
function had no effect on leukocyte rolling flux at any time point in
wild-type or L-selectin-deficient mice. Despite reduced rolling,
leukocyte adhesion and emigration were not measurably reduced in the
L-selectin-deficient mice in this vascular bed. In conclusion,
leukocyte rolling is L-selectin-dependent post-Ag challenge with
L-selectin and P-selectin sharing overlapping
functions.
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