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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4214-4222.
Prepublished online as a Blood First Edition Paper on August 17, 2006; DOI 10.1182/blood-2006-04-017160.
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Submitted April 13, 2006
Accepted August 2, 2006
CD157 plays a pivotal role in neutrophil transendothelial migration
Erika Ortolan, Elena Vittoria Tibaldi, Bruna Ferranti, Luisa Lavagno, Giovanni Garbarino, Rosario Notaro, Lucio Luzzatto, Fabio Malavasi, and Ada Funaro*
University of Torino and Research Center for Experimental Medicine (CeRMS), Torino, Italy
University of Torino, Torino, Italy
Department of Internal Medicine, University of Torino, Torino, Italy
National Institute for Cancer Research, Genova, Italy
University of Genova, Genova, Italy
* Corresponding author; email: ada.funaro{at}unito.it.
Paracellular diapedesis, a key step in leukocyte recruitment to site of inflammation, occurs at endothelial junctions and is regulated by highly coordinated interactions between leukocytes and endothelium. We found that CD157, a glycosilphosphatidylinositol-anchored ectoenzyme belonging to the NADase/ADP-ribosyl cyclase family, plays a crucial role for neutrophil diapedesis, since its ligation with specific mAb (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 towards junctions where they eventually stop without transmigrate. These findings are relevant in vivo, indeed CD157-deficient neutrophils obtained from patients with paroxysmal nocturnal hemoglobinuria are characterized by a severely impaired diapedesis.
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