CD157 is an important mediator of neutrophil adhesion and migration.
CD157, a glycosylphosphatidylinositol (GPI)-anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca(2+) concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]-ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)-differentiated (CD157(+)/CD38(-)) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and beta(2) integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formyl-methionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation.
Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, 10126 Torino, Italy. ada.funaro@unito.it
Ada
A
Funaro
Erika
E
Ortolan
Bruna
B
Ferranti
Lucia
L
Gargiulo
Rosario
R
Notaro
Lucio
L
Luzzatto
Fabio
F
Malavasi
D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000502:physiology*; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D058851:GPI-Linked Proteins; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D005810:Multigene Family; D009504:Neutrophils / Q000502:physiology*; D012016:Reference Values
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2