Evidence map›Paper›PMID 41165762›Full record

ArticleJCI insight2025

Macrophage-specific therapy blocks the lung's mechanosensitive immune response to alveolar distension.

Liberty Mthunzi, Mohammad N Islam, Galina A Gusarova, Brian Karolewski, Sunita Bhattacharya, Jahar Bhattacharya

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Liberty MthunziLung Biology Laboratory; Division of Pulmonary, Allergy, and Critical Care Medicine; Department of Medicine; Vagelos College of Physicians and Surgeons; and.
Mohammad N IslamLung Biology Laboratory; Division of Pulmonary, Allergy, and Critical Care Medicine; Department of Medicine; Vagelos College of Physicians and Surgeons; and.
Galina A GusarovaLung Biology Laboratory; Division of Pulmonary, Allergy, and Critical Care Medicine; Department of Medicine; Vagelos College of Physicians and Surgeons; and.
Brian KarolewskiInstitute of Comparative Medicine, Columbia University Irving Medical Center, Columbia University, New York, New York, USA.
Sunita BhattacharyaLung Biology Laboratory; Division of Pulmonary, Allergy, and Critical Care Medicine; Department of Medicine; Vagelos College of Physicians and Surgeons; and.
Jahar BhattacharyaLung Biology Laboratory; Division of Pulmonary, Allergy, and Critical Care Medicine; Department of Medicine; Vagelos College of Physicians and Surgeons; and.

Funding

MICROPUNCTURE STUDIES OF LUNG, WATER AND SOLUTE EXCHANGER01HL036024 · NHLBI · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI BHATTACHARYA, JAHAR · 1985 to 2025
$7.0M
MICROPUNCTURE STUDIES OF LUNG WATER SOLUTE EXCHANGER37HL036024 · NHLBI · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI BHATTACHARYA, JAHAR · 1998 to 2007
$3.0M
Intravenously injected mesenchymal stromal cells protect against Acute Lung Injury by transferring mitochondria to restore endothelial functionR01HL175058 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI Mohammad Naimul Islam · 2025 to 2026
$1.5M
NHLBI NIH HHS R01 HL036024NHLBI NIH HHS R01 HL175058NHLBI NIH HHS R37 HL036024
6 · The paper itself

Abstract

The lung's mechanosensitive immune response to alveolar overdistension impedes ventilation therapy for hypoxemic respiratory failure. Though mechanistically unclear, the prevailing hypothesis is that the immune response results when alveolar overdistension stretches alveolar macrophages (AMs). Since this hypothesis is untested in live lungs, we optically imaged live mouse alveoli to detect alveolus-adherent, sessile AMs that communicate with the alveolar epithelium through connexin 43-containing (Cx43-containing) gap junctions. Alveolar hyperinflation did not stretch the AMs, but it increased AM Ca2+. AM-specific Cx43 deletion blocked the Ca2+ response, as well as lung injury due to mechanical ventilation at high tidal volume (HTV). HTV-induced injury was also inhibited by AM-targeted delivery of liposomes containing the inhibitor of endosomal Ca2+ release, xestospongin C. We conclude Cx43- and Ca2+-dependent AM-epithelium interactions determine the lung's mechanosensitive immunity, providing a basis for therapy for ventilator-induced lung injury.

Indexed as

LungMacrophages, AlveolarPulmonary AlveoliVentilator-Induced Lung InjuryAnimalsCalciumConnexin 43Disease Models, AnimalGap JunctionsMaleMiceMice, Inbred C57BLRespiration, ArtificialCalciumConnexin 43GJA1 protein, mouseCalcium signalingCell biologyInflammationMacrophagesPulmonology

Identifiers

PMID41165762
PMCPMC12890529

What Socratic 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 Socratic graph.