CD157 plays a pivotal role in neutrophil transendothelial migration.
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.
Ortolan
Erika
E
Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Medical School, Via Santena 19, 10126 Torino, Italy.
Tibaldi
Elena V
EV
Ferranti
Bruna
B
Lavagno
Luisa
L
Garbarino
Giovanni
G
Notaro
Rosario
R
Luzzatto
Lucio
L
Malavasi
Fabio
F
Funaro
Ada
A
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*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2