title: CD157 plays a pivotal role in neutrophil transendothelial migration.
abstract: Paracellular diapedesis, a key step in leukocyte recruitment to the site of inflammation, occurs at endothelial junctions and is regulated by highly coordinated interactions between leukocytes and endothelium. We found that CD157, a glycosylphosphatidylinositol-anchored ectoenzyme belonging to the NADase/ADP-ribosyl cyclase family, plays a crucial role for neutrophil diapedesis, because its ligation with specific monoclonal antibodies (both on neutrophils or endothelial cells) results in altered neutrophil movement on the apical surface of endothelium and, ultimately, in loss of diapedesis. Real-time microscopy revealed that CD157 behaves as a sort of compass during the interaction between neutrophils and endothelial cells; indeed, following CD157 ligation, neutrophils appear disoriented, meandering toward junctions where they eventually stop without transmigrating. These findings are relevant in vivo because CD157-deficient neutrophils obtained from patients with paroxysmal nocturnal hemoglobinuria are characterized by a severely impaired diapedesis.
authors.affiliation: Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Medical School, Via Santena 19, 10126 Torino, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Ortolan
authors.forename: Elena V
authors.initials: EV
authors.lastname: Tibaldi
authors.forename: Bruna
authors.initials: B
authors.lastname: Ferranti
authors.forename: Luisa
authors.initials: L
authors.lastname: Lavagno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Garbarino
authors.forename: Rosario
authors.initials: R
authors.lastname: Notaro
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007152:Immunologic Capping; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2