title: 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.
authors.affiliation: Immunology Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1. woodman@acs.ucalgary.ca
authors.forename: R C
authors.initials: RC
authors.lastname: Woodman
authors.forename: B
authors.initials: B
authors.lastname: Johnston
authors.forename: M J
authors.initials: MJ
authors.lastname: Hickey
authors.forename: D
authors.initials: D
authors.lastname: Teoh
authors.forename: P
authors.initials: P
authors.lastname: Reinhardt
authors.forename: B Y
authors.initials: BY
authors.lastname: Poon
authors.forename: P
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D051917:Leukosialin; D051379:Mice; D012795:Sialoglycoproteins / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse