Evidence map›Paper›PMID 38961477›Full record

ArticleImmunity & ageing : I & A2024

Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction.

Carola Ledderose, Eleftheria-Angeliki Valsami, Mark Elevado, Qing Liu, Brennan Giva, Julian Curatolo, Joshua Delfin, Reem Abutabikh, Wolfgang G Junger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity & ageing : I & A, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

9 authors.

Carola LedderoseDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Eleftheria-Angeliki ValsamiDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mark ElevadoDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Qing LiuDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Brennan GivaDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Julian CuratoloDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Joshua DelfinDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Reem AbutabikhDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA.
Wolfgang G JungerDepartment of Surgery, University of California, San Diego Health, 9452 Medical Ctr Dr, La Jolla, San Diego, CA, 92037, USA. wgjunger@health.ucsd.edu.

Funding

Metabolic and purinergic immune regulationR35GM136429 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JUNGER, WOLFGANG G · 2020 to 2024
$2.3M
Role of purinergic signaling in pediatric multi-organ failureR01HD098363 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JUNGER, WOLFGANG G · 2019 to 2023
$2.0M
NICHD NIH HHS R01 HD098363NIGMS NIH HHS R35 GM136429NIH HHS R35 GM-136429
6 · The paper itself

Abstract

backgroundThe function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals.

resultsBacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca

conclusionsOur findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

Indexed as

AgingATP hydrolysisMiceNeutrophil dysfunctionPurinergic signaling

Identifiers

PMID38961477
PMCPMC11221114

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.