Rc. Woodman et al., The functional paradox of CD43 in leukocyte recruitment: A study using CD43-deficient mice, J EXP MED, 188(11), 1998, pp. 2181-2186
Although there is considerable evidence implicating a role for CD43 (leukos
ialin) in leukocyte cell-cell interactions, its precise function remains un
certain. Using CD43-deficient mice (CD43(-/-)) and intravital microscopy to
directly visualize leukocyte interactions in vivo, we investigated the rol
e of CD43 in leukocyte-endothelial cell interactions within the cremasteric
microcirculation under flow conditions. Our studies demonstrated significa
ntly enhanced leukocyte rolling and adhesion after chemotactic stimuli in C
D43(-/-) mice compared with wild type mice. Using an in vitro flow chamber,
we established that the enhanced rolling interactions of CD43(-/-) leukocy
tes, primarily neutrophils, were also observed using immobilized E-selectin
as a substrate, suggesting that passive processes related to steric hindra
nce or charge repulsion were Likely mechanisms. Despite increased adhesion
and rolling interactions by CD43(-/-) leukocytes, we uncovered a previously
unrecognized impairment of CD43(-/-) leukocytes to infiltrate tissues. Oys
ter glycogen-induced neutrophil and monocyte infiltration into the peritone
um was significantly reduced in CD43(-/-) mice. In response to platelet act
ivating factor, CD43(-/-) leukocytes were impaired in their ability to emig
rate out of the vasculature. These results suggest that leukocyte CD43 has
a dual function in leukocyte-endothelial interactions. In addition to its r
ole as a passive nonspecific functional barrier, CD43 also facilitates emig
ration of leukocytes into tissues.