PMID- 15328157 OWN - NLM STAT- MEDLINE DCOM- 20050324 LR - 20220317 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 104 IP - 13 DP - 2004 Dec 15 TI - CD157 is an important mediator of neutrophil adhesion and migration. PG - 4269-78 AB - 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. FAU - Funaro, Ada AU - Funaro A AD - Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, 10126 Torino, Italy. ada.funaro@unito.it FAU - Ortolan, Erika AU - Ortolan E FAU - Ferranti, Bruna AU - Ferranti B FAU - Gargiulo, Lucia AU - Gargiulo L FAU - Notaro, Rosario AU - Notaro R FAU - Luzzatto, Lucio AU - Luzzatto L FAU - Malavasi, Fabio AU - Malavasi F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040824 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (GPI-Linked Proteins) RN - 0 (Membrane Proteins) RN - 0 (phosphatidylinositol glycan-class A protein) RN - EC 3.2.2.5 (ADP-ribosyl Cyclase) RN - EC 3.2.2.5 (ADP-ribosyl cyclase 2) SB - IM MH - ADP-ribosyl Cyclase/genetics/*physiology MH - Antigens, CD/genetics/*physiology MH - Cell Adhesion/*physiology MH - Cell Division/physiology MH - Chemotaxis, Leukocyte/*physiology MH - GPI-Linked Proteins MH - Humans MH - Membrane Proteins/*blood MH - Multigene Family MH - Neutrophils/*physiology MH - Reference Values EDAT- 2004/08/26 05:00 MHDA- 2005/03/25 09:00 CRDT- 2004/08/26 05:00 PHST- 2004/08/26 05:00 [pubmed] PHST- 2005/03/25 09:00 [medline] PHST- 2004/08/26 05:00 [entrez] AID - S0006-4971(20)49075-5 [pii] AID - 10.1182/blood-2004-06-2129 [doi] PST - ppublish SO - Blood. 2004 Dec 15;104(13):4269-78. doi: 10.1182/blood-2004-06-2129. Epub 2004 Aug 24.