The functional paradox of CD43 in leukocyte recruitment: A study using CD43-deficient mice

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.