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Coronin-1 Is Associated with Neutrophil Survival and Is Cleaved during Apoptosis: Potential Implication in Neutrophils from Cystic Fibrosis Patients¹

Sandra Moriceau^2,*, Chahrazade Kantari^2,*, Julie Mocek^2,*, Noélie Davezac, Julie Gabillet^*, Ida Chiara Guerrera^*, Frank Brouillard^*, Danielle Tondelier^*, Isabelle Sermet-Gaudelus, Claire Danel, Gérard Lenoir, Soizic Daniel^*, Aleksander Edelman^* and Véronique Witko-Sarsat^3,*

^* Institut National de la Santé et de la Recherche Médicale Unité 845, Université René Descartes, Hôpital Necker, Paris, France; Centre National de la Recherche Scientifique FRE 2937 Institut André Lwoff, Villejuif, Université Paris-sud, Paris, France; Service de Pédiatrie Générale, Hôpital Necker-Enfants Malades, Paris, France; and Service d’anatomopathologie, Hôpital Bichat, Paris, France

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by research funding from the European project NEUPROCF and the associations "Mucoviscidose ABCF," "Vaincre La Mucoviscidose," and the Chancellerie des Universités (Legs Poix).

² S.M., C.K., and J.M. contributed equally to the work.

³ Address correspondence and reprint requests to Dr. Véronique Witko-Sarsat, Institut National de la Santé et de la Recherche Médicale Unité 845, Hôpital Necker, 149, rue de Sèvres, 75015 Paris Cedex 15, France. E-mail address: veronique.witko{at}inserm.fr

⁴ Abbreviations used in this paper: CF, cystic fibrosis; 7-AAD, 7-aminoactinomycin D; DIOC6, 3,3'dihexyloacarbocyanine iodide; DMF, dimethylformamide; HA, hemagglutinin A; PFA, paraformaldehyde; pI, isoelectric point; PVDF, polyvinylidene fluoride.