The Functional Paradox of CD43 in Leukocyte Recruitment: A Study Using CD43-deficient Mice

Abstract

Although there is considerable evidence implicating a role for CD43 (leukosialin) in leukocyte cell-cell interactions, its precise function remains uncertain. Using CD43-deficient mice (CD43(-/-)) and intravital microscopy to directly visualize leukocyte interactions in vivo, we investigated the role of CD43 in leukocyte-endothelial cell interactions within the cremasteric microcirculation under flow conditions. Our studies demonstrated significantly enhanced leukocyte rolling and adhesion after chemotactic stimuli in CD43(-/-) mice compared with wild type mice. Using an in vitro flow chamber, we established that the enhanced rolling interactions of CD43(-/-) leukocytes, primarily neutrophils, were also observed using immobilized E-selectin as a substrate, suggesting that passive processes related to steric hindrance 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. Oyster glycogen-induced neutrophil and monocyte infiltration into the peritoneum was significantly reduced in CD43(-/-) mice. In response to platelet activating factor, CD43(-/-) leukocytes were impaired in their ability to emigrate out of the vasculature. These results suggest that leukocyte CD43 has a dual function in leukocyte-endothelial interactions. In addition to its role as a passive nonspecific functional barrier, CD43 also facilitates emigration of leukocytes into tissues.