J Innate Immun 2010;2:260–266
(DOI:10.1159/000295791)

In Cystic Fibrosis Homozygotes and Heterozygotes, Neutrophil Apoptosis Is Delayed and Modulated by Diamide or Roscovitine: Evidence for an Innate Neutrophil Disturbance

Moriceau S.a · Lenoir G.b · Witko-Sarsat V.a, c
aINSERM U845 and bDepartment of General Pediatrics, Necker Hospital, cINSERM U1016-CNRS UMR 8104-Université Paris Descartes, Cochin Hospital, Paris, France
email Corresponding Author


 goto top of outline Key Words

  • Apoptosis
  • Cystic fibrosis transmembrane regulator
  • Diamide
  • Inflammation
  • Neutrophil
  • Roscovitine

 goto top of outline Abstract

Cystic fibrosis (CF) is a chronic inflammatory lung disease characterized by polymorphonuclear neutrophil (PMN)-dominated airway inflammation. Defective apoptosis might explain PMN persistence at these inflammation sites. We previously reported that in CF patients PMN underwent delayed apoptosis, which was not always related to their infectious state and independent of the type of CF transmembrane regulator (CFTR) mutation. To understand the role of infection and PMN apoptosis in CF, PMN apoptosis was investigated in CF parents who are obligate heterozygotes for the CFTR mutation but without chronic bacterial infection. They also demonstrated delayed PMN apoptosis compared with healthy controls, as assessed by annexin-V labeling and caspase-3 cleavage. Diamide, a direct thiol-oxidizing agent, potentiated PMN apoptosis in controls and CF patients, resulting in similar levels of constitutive and Fas-potentiated apoptosis. The cyclin-dependent kinase inhibitor roscovitine provided another approach to restore normal PMN apoptosis. However, the selective CFTR inhibitor CFTRInh172 did not affect PMN apoptosis in control subjects. Apparently, the dysregulation of CF PMN is not only a consequence of the chronic infectious state in CF children but might also be related to CF ‘intrinsic’ factors. Restoration of normal PMN apoptosis by cellular redox modulation or roscovitine opens new research avenues to decrease PMN-mediated inflammation in CF.

Copyright © 2010 S. Karger AG, Basel


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 goto top of outline Author Contacts

Dr. Véronique Witko-Sarsat
INSERM U1016, Cochin Institute, Immunology-Hematology Department
27, rue du Faubourg Saint-Jacques
FR–75014 Paris (France)
Tel. +33 1 40 51 66 56, Fax +33 1 40 51 65 35, E-Mail veronique.witko@inserm.fr


 goto top of outline Article Information

Received: December 23, 2009
Accepted after revision: January 11, 2010
Published online: March 10, 2010
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 34


 goto top of outline Publication Details

Journal of Innate Immunity

Vol. 2, No. 3, Year 2010 (Cover Date: April 2010)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


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