Document Detail

Involvement of the cystine transport system xc- in the macrophage-induced glutamate-dependent cytotoxicity to neurons.
MedLine Citation:
PMID:  8144936     Owner:  NLM     Status:  MEDLINE    
Macrophages have been found to release glutamate and thereby induce neuronal cell death by excitotoxicity, a mechanism that seems to be operative in various neurologic diseases. In this study, it is shown that the presence of both cystine and glutamine in the culture medium is indispensable for brain macrophages to release glutamate and to cause neuronal cell death. Furthermore, release of glutamate requires protein synthesis since cycloheximide prevented accumulation of the neurotoxic molecule in supernatants of microglial cell cultures. Aminoadipate, which was shown to inhibit the uptake of cystine by system xc- in fibroblasts, efficiently reduced the release of glutamate. The requirement of glutamine and cystine for the release of glutamate by microglial cells as well as the inhibitory effect observed with aminoadipate shows the transport system xc- to be essential for the release of the excitotoxin glutamate by microglial cells. Phagocytosis of zymosan particles and stimulation with different bacterial components, such as LPS, protein A, tuberculin, and Staphylococcus enterotoxin A increased glutamate release two- to threefold above basal values. In addition, the effect of bacterial components was mimicked by TNF-alpha, but not by IL-1 and IL-6. Cytokines known to deactivate macrophages, such as TGF-beta, IL-4, and IL-10, did not affect the transport system xc- in microglial cells. However, dexamethasone suppressed the glutamate release up to 50%.
D Piani; A Fontana
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  152     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-04-29     Completed Date:  1994-04-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3578-85     Citation Subset:  AIM; IM    
Department of Internal Medicine, University Hospital Zurich, Switzerland.
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MeSH Terms
Biological Transport / drug effects
Cycloheximide / pharmacology
Cystine / metabolism*
Dexamethasone / pharmacology
Glutamates / toxicity*
Glutamine / metabolism
Interleukin-1 / pharmacology
Interleukin-10 / pharmacology
Interleukin-4 / pharmacology
Interleukin-6 / pharmacology
Macrophages / physiology*
Mice, Inbred ICR
Microglia / physiology*
Neurons / cytology*,  drug effects
Transforming Growth Factor beta / pharmacology
Tumor Necrosis Factor-alpha / pharmacology
Reg. No./Substance:
0/Glutamates; 0/Interleukin-1; 0/Interleukin-6; 0/Transforming Growth Factor beta; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10; 207137-56-2/Interleukin-4; 50-02-2/Dexamethasone; 56-85-9/Glutamine; 56-89-3/Cystine; 66-81-9/Cycloheximide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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