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

Richard C. Woodman, Brent Johnston, Michael J. Hickey, Diane Teoh, Paul Reinhardt, Betty Y. Poon, Paul Kubes

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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.

Original languageEnglish
Pages (from-to)2181-2186
Number of pages6
JournalJournal of Experimental Medicine
Volume188
Issue number11
DOIs
Publication statusPublished - 7 Dec 1998
Externally publishedYes

Keywords

  • Antiadhesive
  • CD43
  • Emigration
  • Leukocytes
  • Recruitment

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