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Infection and Immunity, August 2006, p. 4708-4714, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.02066-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Expression and Antimicrobial Function of Bactericidal Permeability-Increasing Protein in Cystic Fibrosis Patients

Diana Aichele,{dagger} Markus Schnare,{dagger} Marc Saake, Martin Röllinghoff, and Andre Gessner*

Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Universität Erlangen-Nürnberg, Wasserturmstraße 3, 91054 Erlangen, Germany

Received 22 December 2005/ Returned for modification 22 February 2006/ Accepted 23 May 2006

In cystic fibrosis (CF), the condition limiting the prognosis of affected children is the chronic obstructive lung disease accompanied by chronic and persistent infection with mostly mucoid strains of Pseudomonas aeruginosa. The majority of CF patients have antineutrophil cytoplasmic antibodies (ANCA) primarily directed against the bactericidal permeability-increasing protein (BPI) potentially interfering with antimicrobial effects of BPI. We analyzed the expression of BPI in the airways of patients with CF. In their sputum samples or bronchoalveolar lavage specimens, nearly all patients expressed BPI mRNA and protein, which were mainly products of neutrophil granulocytes as revealed by intracellular staining and subsequent flow cytometry. Repeated measurements revealed consistent individual BPI expression levels during several months quantitatively correlating with interleukin-8. In vitro, P. aeruginosa isolates from CF patients initiated the rapid release of BPI occurring independently of protein de novo syntheses. Furthermore, purified natural BPI as well as a 27-mer BPI-derived peptide displayed antimicrobial activity against even patient-derived mucoid P. aeruginosa strains and bacteria resistant against all antibiotics tested. Thus, BPI that is functionally active against mucoid P. aeruginosa strains is expressed in the airways of CF patients but may be hampered by autoantibodies, resulting in chronic infection.

* Corresponding author. Mailing address: Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Wasserturmstr. 3, D-91054 Erlangen, Germany. Phone: 49-9131-85-25 80. Fax: 49-9131-85 2 1001. E-mail: gessner{at}mikrobio.med.uni-erlangen.de.

Editor: J. N. Weiser

{dagger} These authors contributed equally to this work.

Infection and Immunity, August 2006, p. 4708-4714, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.02066-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lachenal, F., Nkana, K., Nove-Josserand, R., Fabien, N., Durieu, I. (2009). Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis. Eur Respir J 34: 1079-1085 [Abstract] [Full Text]  
  • Wittmann, I., Schonefeld, M., Aichele, D., Groer, G., Gessner, A., Schnare, M. (2008). Murine Bactericidal/Permeability-Increasing Protein Inhibits the Endotoxic Activity of Lipopolysaccharide and Gram-Negative Bacteria. J. Immunol. 180: 7546-7552 [Abstract] [Full Text]  


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