Coronin-1 Is Associated with Neutrophil Survival and Is Cleaved during Apoptosis: Potential Implication in Neutrophils from Cystic Fibrosis Patients

• Published in: The Journal of immunology (1950) 2009-06, Vol.182 (11), p.7254-7263
• Main Authors: Moriceau, Sandra, Kantari, Chahrazade, Mocek, Julie, Davezac, Noelie, Gabillet, Julie, Guerrera, Ida Chiara, Brouillard, Frank, Tondelier, Danielle, Sermet-Gaudelus, Isabelle, Danel, Claire, Lenoir, Gerard, Daniel, Soizic, Edelman, Aleksander, Witko-Sarsat, Veronique
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Survival; Cystic Fibrosis - pathology; Cytosol - chemistry; Humans; Hydrolysis; Inflammation; Microfilament Proteins - analysis; Microfilament Proteins - metabolism; Microfilament Proteins - physiology; Mitochondria - physiology; Neutrophils - cytology; Neutrophils - pathology; Proteomics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0803312

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.