Evidence map›Paper›PMID 10816516›Full record

ArticleInfection and immunity2000

Cooperation between reactive oxygen and nitrogen intermediates in killing of Rhodococcus equi by activated macrophages.

P A Darrah, M K Hondalus, Q Chen, H Ischiropoulos, D M Mosser

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 134 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

P A DarrahDepartment of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
M K Hondalus
Q Chen
H Ischiropoulos
D M Mosser
Temple University · USUniversity of Pennsylvania · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rhodococcus equi is a facultative intracellular bacterium of macrophages which can infect immunocompromised humans and young horses. In the present study, we examine the mechanism of host defense against R. equi by using a murine model. We show that bacterial killing is dependent upon the presence of gamma interferon (IFN-gamma), which activates macrophages to produce reactive nitrogen and oxygen intermediates. These two radicals combine to form peroxynitrite (ONOO(-)), which kills R. equi. Mice deficient in the production of either the high-output nitric oxide pathway (iNOS(-/-)) or the oxidative burst (gp91(phox-/-)) are more susceptible to lethal R. equi infection and display higher bacterial burdens in their livers, spleens, and lungs than wild-type mice. These in vivo observations, which implicate both nitric oxide (NO) and superoxide (O(2)(-)) in bacterial killing, were reexamined in cell-free radical-generating assays. In these assays, R. equi remains fully viable following prolonged exposure to high concentrations of either nitric oxide or superoxide, indicating that neither compound is sufficient to mediate bacterial killing. In contrast, brief exposure of bacteria to ONOO(-) efficiently kills virulent R. equi. The intracellular killing of bacteria in vitro by activated macrophages correlated with the production of ONOO(-) in situ. Inhibition of nitric oxide production by activated macrophages by using N(G)-monomethyl-L-arginine blocks their production of ONOO(-) and weakens their ability to control rhodococcal replication. These studies indicate that peroxynitrite mediates the intracellular killing of R. equi by IFN-gamma-activated macrophages.

Indexed as

Actinomycetales InfectionsAnimalsFree RadicalsInterferon-gammaMacrophage ActivationMacrophagesMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Mutant StrainsNADPH Oxidase 2NADPH OxidasesNitratesNitric Oxide SynthaseNitric Oxide Synthase Type IICYBB protein, humanFree RadicalsInterferon-gammaMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNitratesNitric Oxide SynthaseNitric Oxide Synthase Type IINitrogen OxidesNos2 protein, mouseperoxynitric acidReactive Oxygen Species

Identifiers

PMID10816516
PMCPMC97647
OpenAlexW2019586445

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.