title: CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin.
abstract: The activation of endothelial cells is critical to initiating an inflammatory response. Activation induces the fusion of Weibel-Palade Bodies (WPB) with the plasma membrane, thus transferring P-selectin and VWF to the cell surface, where they act in the recruitment of leukocytes and platelets, respectively. CD63 has long been an established component of WPB, but the functional significance of its presence within an organelle that acts in inflammation and hemostasis was unknown. We find that ablating CD63 expression leads to a loss of P-selectin-dependent function: CD63-deficient HUVECs fail to recruit leukocytes, CD63-deficient mice exhibit a significant reduction in both leukocyte rolling and recruitment and we show a failure of leukocyte extravasation in a peritonitis model. Loss of CD63 has a similar phenotype to loss of P-selectin itself, thus CD63 is an essential cofactor to P-selectin.
authors.affiliation: Medical Research Council (MRC) Laboratory for Molecular Cell Biology, University College London (UCL), London, UK.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Doyle
authors.forename: Victoria
authors.initials: V
authors.lastname: Ridger
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraro
authors.forename: Mark
authors.initials: M
authors.lastname: Turmaine
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Cutler
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D060149:Tetraspanin 30 / Q000235:genetics / Q000378:metabolism*; D020302:Weibel-Palade Bodies / Q000235:genetics / Q000378:metabolism
chemical_list: C554586:CD63 protein, human; C554587:Cd63 protein, mouse; D019007:P-Selectin; D060149:Tetraspanin 30