HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M500019-MCP200v1 4/10/1591    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bensalem, N. Articles by Edelman, A. Search for Related Content PubMed PubMed Citation Articles by Bensalem, N. Articles by Edelman, A. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 4:1591-1601, 2005.
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Down-regulation of the Anti-inflammatory Protein Annexin A1 in Cystic Fibrosis Knock-out Mice and Patients^*,S

From the ^a INSERM U467, ^d Proteomic Core Facilities, and ^e INSERM U370, Faculté de médecine Necker, Université Paris-Descartes, 156 rue de Vaugirard, Paris F-75015, France, ^c Laboratoire de spectrométrie de masse, Institut de Chimie des Substances Naturelles CNRS, Gif-sur-Yvette F-91198, France, ^f The William Harvey Research Institute, Centre of Biochemical Pharmacology, Barts and The London Queen Mary’s School of Medicine and Dentistry, London EC1M 6BQ, United Kingdom, ^h Service d’Histologie-Biologie Tumorale, Unité Propre Enseignement Supérieur-Equip d’Acceuil 3499, Hôpital Tenon, 4 rue de Chine, Paris F-75020, France, ⁱ Service de Pédiatrie Générale, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris F-75015, France, ^j Centre de Ressources et de Compétence en Mucoviscidose, Groupe Hospitalier Sud Réunion, BP 350, Saint Pierre F-97448, France, and ^k Centre de Ressources et de Compétence en Mucoviscidose, Hôpital d’Enfants, Saint Denis F-97476, France

Cystic fibrosis is a fatal human genetic disease caused by mutations in the CFTR gene encoding a cAMP-activated chloride channel. It is characterized by abnormal fluid transport across secretory epithelia and chronic inflammation in lung, pancreas, and intestine. Because cystic fibrosis (CF) pathophysiology cannot be explained solely by dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR), we applied a proteomic approach (bidimensional electrophoresis and mass spectrometry) to search for differentially expressed proteins between mice lacking cftr (cftr^tm1Unc, cftr^–/–) and controls using colonic crypts from young animals, i.e. prior to the development of intestinal inflammation. By analyzing total proteins separated in the range of pH 6–11, we detected 24 differentially expressed proteins (>2-fold). In this work, we focused on one of these proteins that was absent in two-dimensional gels from cftr^–/– mice. This protein spot (molecular mass, 37 kDa; pI 7) was identified by mass spectrometry as annexin A1, an anti-inflammatory protein. Interestingly, annexin A1 was also undetectable in lungs and pancreas of cftr^–/– mice, tissues known to express CFTR. Absence of this inhibitory mediator of the host inflammatory response was associated with colonic up-regulation of the proinflammatory cytosolic phospholipase A₂. More importantly, annexin A1 was down-regulated in nasal epithelial cells from CF patients bearing homozygous nonsense mutations in the CFTR gene (Y122X, 489delC) and differentially expressed in F508del patients. These results suggest that annexin A1 may be a key protein involved in CF pathogenesis especially in relation to the not well defined field of inflammation in CF. We suggest that decreased expression of annexin A1 contributes to the worsening of the CF phenotype.

^m To whom correspondence may be addressed: INSERM U467, Faculté de médecine, Université Paris-Descartes, 156 rue de Vaugirard, Paris F-75015, France. Tel.: 33-1-40-61-56-21; Fax: 33-1-40-61-55-91; E-mail: edelman@necker.fr

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Z. Cao, C. Li, J. N. Higginbotham, J. L. Franklin, D. L. Tabb, R. Graves-Deal, S. Hill, K. Cheek, W. G. Jerome, L. A. Lapierre, et al. Use of Fluorescence-activated Vesicle Sorting for Isolation of Naked2-associated, Basolaterally Targeted Exocytic Vesicles for Proteomics Analysis Mol. Cell. Proteomics, September 1, 2008; 7(9): 1651 - 1667. [Abstract] [Full Text] [PDF]

				S. D. Reynolds, P. R. Reynolds, J. C. Snyder, F. Whyte, K. J. Paavola, and B. R. Stripp CCSP regulates cross talk between secretory cells and both ciliated cells and macrophages of the conducting airway Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L114 - L123. [Abstract] [Full Text] [PDF]

				M. Scannell, M. B. Flanagan, A. deStefani, K. J. Wynne, G. Cagney, C. Godson, and P. Maderna Annexin-1 and Peptide Derivatives Are Released by Apoptotic Cells and Stimulate Phagocytosis of Apoptotic Neutrophils by Macrophages J. Immunol., April 1, 2007; 178(7): 4595 - 4605. [Abstract] [Full Text] [PDF]

				T. E. Machen Innate immune response in CF airway epithelia: hyperinflammatory? Am J Physiol Cell Physiol, August 1, 2006; 291(2): C218 - C230. [Abstract] [Full Text] [PDF]