title: Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: potential implication in neutrophils from cystic fibrosis patients.
abstract: Because neutrophil apoptosis plays a key role in resolving inflammation, identification of proteins regulating neutrophil survival should provide new strategies to modulate inflammation. Using a proteomic approach, coronin-1 was identified as a cytosolic protein cleaved during neutrophil apoptosis. Coronin-1 is an actin-binding protein that can associate with phagosomes and NADPH oxidase, but its involvement in apoptosis was currently unknown. In coronin-1-transfected PLB985 cells, coronin-1 overexpression did not modify the kinetics of granulocyte differentiation as assessed by CD11b labeling. Concerning apoptosis, increased coronin-1 expression in dimethylformamide-differentiated PLB985 significantly decreased gliotoxin-induced mitochondrial depolarization as compared with controls. Likewise, coronin-1 significantly decreased TRAIL-induced apoptosis with less mitochondrial depolarization, caspase-3 and caspase-9 activities, but not caspase-8 or Bid truncation suggesting that coronin-1 interfered with mitochondria-related events. To validate the prosurvival role of coronin-1 in a pathophysiological condition involving neutrophil-dominated inflammation, neutrophils from cystic fibrosis (CF) patients were studied. Circulating neutrophils from CF patients had more coronin-1 expression assessed by immunoblotting or proteomic analysis of cytosolic proteins. This was associated with a lower apoptosis rate than those from controls evidenced by delayed phosphatidylserine externalization and mitochondria depolarization. In addition, inflammatory neutrophils from CF patients lungs showed an intense coronin-1 immunolabeling. We concluded that coronin-1 could constitute a potential target in resolving inflammation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 845, Université René Descartes, Hôpital Necker, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moriceau
authors.forename: Chahrazade
authors.initials: C
authors.lastname: Kantari
authors.forename: Julie
authors.initials: J
authors.lastname: Mocek
authors.forename: Noélie
authors.initials: N
authors.lastname: Davezac
authors.forename: Julie
authors.initials: J
authors.lastname: Gabillet
authors.forename: Ida Chiara
authors.initials: IC
authors.lastname: Guerrera
authors.forename: Frank
authors.initials: F
authors.lastname: Brouillard
authors.forename: Danielle
authors.initials: D
authors.lastname: Tondelier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet-Gaudelus
authors.forename: Claire
authors.initials: C
authors.lastname: Danel
authors.forename: Gérard
authors.initials: G
authors.lastname: Lenoir
authors.forename: Soizic
authors.initials: S
authors.lastname: Daniel
authors.forename: Aleksander
authors.initials: A
authors.lastname: Edelman
authors.forename: Véronique
authors.initials: V
authors.lastname: Witko-Sarsat
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D003550:Cystic Fibrosis / Q000473:pathology; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation; D008840:Microfilament Proteins / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000473:pathology; D040901:Proteomics
chemical_list: D008840:Microfilament Proteins; C072061:coronin proteins