Nitric oxide production and neurotoxicity mediated by activated microglia from human versus mouse brain

Phillip K. Peterson, Shuxian Hu, W. Robert Anderson, Chun C. Chao

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Recent studies indicate that human macrophages lack a high-output inducible nitric oxide synthase (NOS) antimicrobial system, In the present study, microglial cells derived from fetal human versus neonatal mouse brain were compared in a coculture assay of human and murine neuronal cell injury, Neurotoxicity (reflected by lactate dehydrogenase release and impaired neuronal uptake of [3H)γ-amino butyric acid) and nitric oxide (NO) production (assessed by measurement of nitrite) were observed only in cocultures containing interferon (IFN)-γ-lipopolysaccharide (LPS)-stimulated murine microglia. Cultures of purified human fetal microglia, however, did produce low levels of NO upon stimulation with IFN-γ-LPS, These findings support the proposal that human macrophages have an inefficient IFN-γ-inducible NOS and suggest that in tissues, such as brain, this deficiency could be advantageous for neighboring cells.

Original languageEnglish (US)
Pages (from-to)457-460
Number of pages4
JournalJournal of Infectious Diseases
Volume170
Issue number2
DOIs
StatePublished - Aug 1994

Bibliographical note

Funding Information:
Departments ofMedicine and ofPathology. Hennepin County Medical Center; the Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation; and University ofMinnesota Medical School. Minneapolis, Minnesota

Funding Information:
Financial support: National Institutes of Health (DA-0438I ) and Hennepin Faculty Associates.

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