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PMID: 2496141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron.

The Journal of clinical investigation ·Vol. 83 ·No. 5 ·1989-05-00 ·Pages 1457-65

Byrd TF, Horwitz MA

Abstract

We have investigated the role of iron in the intracellular biology of Legionella pneumophila in human monocytes and in the effector arm of cell-mediated immune defense against this intracellular bacterial pathogen. To determine if L. pneumophila intracellular multiplication is iron dependent, we studied the effect of the iron chelator deferoxamine on L. pneumophila infection of monocytes. Deferoxamine at 15 microM completely inhibited L. pneumophila intracellular multiplication. The inhibitory effect of deferoxamine was reversed with equimolar iron-saturated transferrin but not apotransferrin. To examine the potential role of iron in monocyte activation, we investigated the influence of iron-saturated transferrin on L. pneumophila multiplication in IFN gamma-activated monocytes. Iron transferrin, but not apotransferrin, neutralized the capacity of activated monocytes to inhibit L. pneumophila multiplication. To explore a potential mechanism by which activated monocytes might limit the availability of intracellular iron, we examined transferrin receptor expression on nonactivated and activated monocytes cultured in vitro for 5 d. By fluorescence-activated flow cytometry, activated monocytes exhibited markedly fewer transferrin receptors than nonactivated monocytes. By Scatchard analysis of 125I-transferrin binding to monocytes, nonactivated monocytes had 38,300 +/- 12,700 (mean +/- SE) transferrin binding sites, whereas activated monocytes had 10,300 +/- 1,600, a reduction of 73%. Activated and nonactivated monocytes had a similar mean Kd (1.8 +/- 0.2 nM). This study demonstrates that (a) L. pneumophila intracellular multiplication is iron dependent; (b) activated monocytes inhibit L. pneumophila multiplication by limiting the availability of intracellular iron; and (c) transferrin receptors are downregulated on IFN gamma-activated monocytes.

MeSH Terms
Adult Cytoplasm/microbiology Humans Interferon-gamma/pharmacology Iron/metabolism,physiology Legionella/growth & development Macrophage Activation/drug effects Monocytes/metabolism,physiology Receptors, Transferrin/drug effects,metabolism Signal Transduction/drug effects Transferrin/pharmacology
Chemicals
Receptors, Transferrin Transferrin Interferon-gamma Iron
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Byrd T F
Department of Medicine, School of Medicine, University of California, Los Angeles 90024.
Horwitz M A
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47 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114038
Published
1989-05-00
Pages
1457-65
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303847
Subset
IM
Grants
NIAID NIH HHS · AI-22421 · United States
External Links
PubMed source DOI: 10.1172/JCI114038 PMC Full Text View journal details
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