IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Britigan, B E
Right arrow Articles by Fick, R B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Britigan, B E
Right arrow Articles by Fick, R B, Jr
Infect Immun. 1993 December; 61(12): 5049-5055

Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis.

B E Britigan, M B Hayek, B N Doebbeling and R B Fick Jr

Research Service, University of Iowa College of Medicine, Iowa City 52242.

ABSTRACT

Bacterium- and neutrophil-derived proteases have been suggested to contribute to tissue injury at sites of Pseudomonas aeruginosa infection. Pseudomonas elastase cleavage of transferrin enhances in vitro iron removal from this protein by the P. aeruginosa siderophore pyoverdin. This cleavage also generates new iron chelates which, in contrast to iron bound to transferrin, are able to catalyze formation of the highly cytotoxic hydroxyl radical from neutrophil-derived superoxide and hydrogen peroxide via the Haber-Weiss reaction. In order to determine whether this cleavage occurs in vivo, a chemiluminescence immunoblot system was developed to detect the presence of proteolysis products of transferrin or the related iron-binding protein, lactoferrin. Using this immunoblot system, we detected transferrin and lactoferrin cleavage products in bronchoalveolar lavage (BAL) samples from 21 of 22 and 20 of 21 cystic fibrosis (CF) patients, respectively. Three of eleven and two of nine BAL samples from individuals with other forms of chronic inflammatory lung disease had transferrin and lactoferrin cleavage products, respectively. Each patient in whom such products were detected was also infected with P. aeruginosa. No such products were detected in normal individuals. In the CF patients, there was no clear correlation between the extent of transferrin or lactoferrin cleavage and BAL neutrophil or P. aeruginosa concentration or the disease status of the patient. In contrast, in the non-CF patients with chronic inflammatory lung disease, transferrin and lactoferrin cleavage products were detected only in those BAL samples which contained the greatest concentration of both neutrophils and P. aeruginosa. These data provide evidence that P. aeruginosa- and/or human-derived protease cleavage of transferrin and lactoferrin occurs in vivo in the airways of individuals with CF and other forms of chronic lung disease, suggesting that this process could contribute to P. aeruginosa-associated lung injury in these patients.

Infect Immun. 1993 December; 61(12): 5049-5055




This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1993 by the American Society for Microbiology. All rights reserved.