Evidence map›Paper›PMID 39621452›Full record

ArticleThe journal of trauma and acute care surgery2025

Lung contusion complicated by pneumonia worsens lung injury via the inflammatory effect of alveolar small extracellular vesicles on macrophages and epithelial cells.

Keita Nakatsutsumi, Wooil Choi, William Johnston, Katie Pool, Dong Jun Park, Jessica L Weaver, Raul Coimbra, Brian Eliceiri, Todd W Costantini

Abstract read
In one paragraph

Article in The journal of trauma and acute care surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Keita NakatsutsumiFrom the Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery (K.N., W.C., W.J., K.P., D.P., J.W., B.E., T.C.), UC San Diego School of Medicine, San Diego; Comparative Effectiveness and Clinical Outcomes Research Center (R.C.), Riverside University Health System, Loma Linda University School of Medicine, Riverside, California; and Trauma and Acute Critical Care Center (K.N.), Tokyo Medical and Dental University Hospital, Bunkyo-ku, Tokyo, Japan.ORCID 0000-0001-6140-8761
Wooil Choi
William Johnston
Katie Pool
Dong Jun Park
Jessica L Weaver
Raul Coimbra
Brian Eliceiri
Todd W CostantiniORCID 0000-0002-0215-5327

Funding

Mechanism of action of uniquely human genes in the injury responseR35GM149345 · NIGMS · UNIVERSITY OF MINNESOTA · PI Todd W Costantini · 2023 to 2026
$1.5M
NIGMS NIH HHS R35 GM149345
6 · The paper itself

Abstract

backgroundLung contusion (LC) complicated by pneumonia is associated with a higher risk of acute lung injury (ALI) mediated by activation of immune cells and injury to the lung epithelium. Small extracellular vesicles (sEVs) are essential mediators of cellular crosstalk; however, their role in the development of postinjury ALI remains unclear. We hypothesized that LC complicated by pneumonia increases the pro-inflammatory effect of alveolar sEVs on macrophages and the cytotoxicity of alveolar sEVs to pulmonary epithelial cells, worsening the severity of ALI.

methodsStudies in C57BL/6 mice were designed with four groups: sham, LC, Pneumonia (Pneu), and LC + Pneu. Lung contusion was induced by a cortical controlled impactor, while pneumonia was conducted by intratracheal injection of 10 5 cfu Pseudomonas aeruginosa . Bronchoalveolar lavage fluid (BAL) was harvested 24 hours postinfection, and sEVs were purified by centrifugation and size exclusion chromatography. To evaluate the effect of alveolar sEV on cells, sEVs from each group were cocultured with macrophages (RAW 264.7) to assess cytokine release and lung epithelial cells (MLE 12) to assess epithelial cytotoxicity.

resultsThe LC + Pneu group severely injured lungs histologically and increased the susceptibility to the bacteria. The LC + Pneu group showed higher concentrations of proteins, macrophage inflammatory protein 1-alpha (MIP1α), and intercellular adhesion molecule 1 (ICAM-1) in BAL. MIP1α and ICAM-1 expression in the macrophages increased after incubation with sEVs from the LC + Pneu group. Moreover, the sEVs demonstrated higher cytotoxicity to epithelial cells and increased apoptosis in epithelial cells after incubation with sEVs from the LC + Pneu group.

conclusionLung contusion complicated by pneumonia increased the pro-inflammatory effect of alveolar sEVs on macrophages and the cytotoxicity of alveolar sEVs to pulmonary epithelial cells, worsening the severity of ALI. These results demonstrate the potential importance of alveolar sEVs in lung inflammation following a bacterial infection after trauma.

Indexed as

Acute Lung InjuryContusionsDisease Models, AnimalEpithelial CellsExtracellular VesiclesLung InjuryMice, Inbred C57BLPneumoniaAnimalsBronchoalveolar Lavage FluidMacrophagesMacrophages, AlveolarMaleMice

Identifiers

PMID39621452
PMCPMC12978313

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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.