title: A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo.
abstract: CD99 is a long-known leukocyte antigen that does not belong to any of the known protein families. It was recently found on endothelial cells, where it mediates transendothelial migration of human monocytes and lymphocyte recruitment into inflamed skin in the mouse. Here, we show that CD99L2, a recently cloned, widely expressed antigen of unknown function with moderate sequence homology to CD99, is expressed on mouse leukocytes and endothelial cells. Using antibodies, we found that CD99L2 and CD99 are involved in transendothelial migration of neutrophils in vitro and in the recruitment of neutrophils into inflamed peritoneum. Intravital and electron microscopy of cremaster venules revealed that blocking CD99L2 inhibited leukocyte transmigration through the vessel wall (diapedesis) at the level of the perivascular basement membrane. We were surprised to find that, in contrast to CD99, CD99L2 was not relevant for the extravasation of lymphocytes into inflamed tissue. Although each protein promoted cell aggregation of transfected cells, endothelial CD99 and CD99L2 participated in neutrophil extravasation independent of these proteins on neutrophils. Our results establish CD99L2 as a new endothelial surface protein involved in neutrophil extravasation. In addition, this is the first evidence for a role of CD99 and CD99L2 in the process of leukocyte diapedesis in vivo.
authors.affiliation: Institute of Cell Biology, Zentrum für Molekularbiologie der Entzündung (ZMBE), Interdisziplinäres Klinisches Forschungszentrum Münster, University of Münster, Münster, Germany.
authors.forename: M Gabriele
authors.initials: MG
authors.lastname: Bixel
authors.forename: Björn
authors.initials: B
authors.lastname: Petri
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Khandoga
authors.forename: Andrej
authors.initials: A
authors.lastname: Khandoga
authors.forename: Karen
authors.initials: K
authors.lastname: Wolburg-Buchholz
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Sigrid
authors.initials: S
authors.lastname: März
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry*; D004730:Endothelium, Vascular; D007249:Inflammation / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D014699:Venules / Q000166:cytology
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C522605:Cd99 protein, mouse