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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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PHAGOCYTES

CD157 plays a pivotal role in neutrophil transendothelial migration

Erika Ortolan, Elena V. Tibaldi, Bruna Ferranti, Luisa Lavagno, Giovanni Garbarino, Rosario Notaro, Lucio Luzzatto, Fabio Malavasi, and Ada Funaro

From the Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy; Research Center for Experimental Medicine (CeRMS), Torino, Italy; Department of Internal Medicine, University of Torino, Torino, Italy; National Institute for Cancer Research, Genova, Italy; and University of Genova, Genova, Italy.

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.


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