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: Sandra Moriceau, Chahrazade Kantari, Julie Mocek, Noélie Davezac, Julie Gabillet, Ida Chiara Guerrera, Frank Brouillard, Danielle Tondelier, Isabelle Sermet-Gaudelus, Claire Danel, Gérard Lenoir, Soizic Daniel, Aleksander Edelman, Véronique Witko-Sarsat
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 11 Pg. 7254-63 (Jun 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19454722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Microfilament Proteins
• coronin proteins

Topics

• Apoptosis
• Cell Survival
• Cystic Fibrosis (pathology)
• Cytosol (chemistry)
• Humans
• Hydrolysis
• Inflammation
• Microfilament Proteins (analysis, metabolism, physiology)
• Mitochondria (physiology)
• Neutrophils (cytology, pathology)
• Proteomics