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

B. E. Britigan, M. B. Hayek, Bradley Doebbeling, R. B. Fick

Research output: Contribution to journalArticle

109 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5049-5055
Number of pages7
JournalInfection and Immunity
Volume61
Issue number12
StatePublished - 1993
Externally publishedYes

Fingerprint

Lactoferrin
Transferrin
Cystic Fibrosis
Pseudomonas aeruginosa
Lung
Bronchoalveolar Lavage
Neutrophils
Lung Diseases
Peptide Hydrolases
Iron
Iron-Binding Proteins
Iron Chelating Agents
Pseudomonas Infections
Siderophores
Pancreatic Elastase
Lung Injury
Pseudomonas
Luminescence
Superoxides
Hydroxyl Radical

ASJC Scopus subject areas

  • Immunology

Cite this

Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. / Britigan, B. E.; Hayek, M. B.; Doebbeling, Bradley; Fick, R. B.

In: Infection and Immunity, Vol. 61, No. 12, 1993, p. 5049-5055.

Research output: Contribution to journalArticle

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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.",
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AU - Fick, R. B.

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