J. Exp. Med., Volume 188, Number 11, December 7, 1998 2181-2186

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

By Richard C. Woodman,^* Brent Johnston,^* Michael J. Hickey,^* Diane Teoh,^* Paul Reinhardt,^* Betty Y. Poon,^* and Paul Kubes^*§

From the ^* Immunology Research Group, the  Department of Medicine, and the ^§ Department of Physiology and Biophysics, University of Calgary, Calgary,  Alberta, Canada T2N 4N1

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.

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