Coronin-1 is associated with neutrophil survival and is cleaved during apoptosis: potential implication in neutrophils from cystic fibrosis patients.
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.
Moriceau
Sandra
S
Institut National de la Santé et de la Recherche Médicale Unité 845, Université René Descartes, Hôpital Necker, Paris, France.
Kantari
Chahrazade
C
Mocek
Julie
J
Davezac
Noélie
N
Gabillet
Julie
J
Guerrera
Ida Chiara
IC
Brouillard
Frank
F
Tondelier
Danielle
D
Sermet-Gaudelus
Isabelle
I
Danel
Claire
C
Lenoir
Gérard
G
Daniel
Soizic
S
Edelman
Aleksander
A
Witko-Sarsat
Véronique
V
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
D008840:Microfilament Proteins; C072061:coronin proteins