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PMID: 1655825 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation.

The Journal of clinical investigation ·Vol. 88 ·No. 4 ·1991-10-00 ·Pages 1092-102

Britigan BE, Edeker BL

Abstract

In vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (.O2-) and hydrogen peroxide (H2O2). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCl were added to a hypoxanthine/xanthine oxidase .O2-/H2O2 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastase-treated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2- or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCl treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCl if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOCl. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury.

MeSH Terms
Apoproteins/metabolism Binding Sites Endopeptidases/pharmacology Humans Hydroxides/metabolism Hydroxyl Radical Hypochlorous Acid/pharmacology Lactoferrin/metabolism Leukocyte Elastase Neutrophils/physiology Pancreatic Elastase/pharmacology Pseudomonas/enzymology Transferrin/metabolism
Chemicals
Apoproteins Hydroxides Transferrin apolactoferrin apotransferrin Hydroxyl Radical Hypochlorous Acid Endopeptidases Lactoferrin Pancreatic Elastase Leukocyte Elastase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Britigan B E
Research Service, Veterans Administration Medical Center, Iowa City, Iowa.
Edeker B L
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115408
Published
1991-10-00
Pages
1092-102
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295559
Subset
IM
Grants
NIAID NIH HHS · AI 28412 · United States
NHLBI NIH HHS · HL 44275 · United States
External Links
PubMed source DOI: 10.1172/JCI115408 PMC Full Text View journal details
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