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Macrophage Characteristics Following Adaptation to Repeated Chlorine Exposures

2025· article· en· W4410272160 on OpenAlexaff
Tomohiro Nishizawa, Rui Sun, Arina Morozan, Suhkneung Pyo, Shijia Wang, Savannah Dunberry, J.J. Tan, Toby K. McGovern, James G. Martin

Bibliographic record

VenueAmerican Journal of Respiratory and Critical Care Medicine · 2025
Typearticle
Languageen
FieldMedicine
TopicMedicinal Plant Studies
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsMedicineAdaptation (eye)ChlorineMacrophageImmunologyNeuroscienceBiochemistryBiologyIn vitro

Abstract

fetched live from OpenAlex

Abstract Rationale: Mice exposed to repeated chlorine gas exposures demonstrate a rapid adaptation to the exposure, with a reduction in airway inflammation and airway hyperresponsiveness to inhaled aerosols of methacholine. A previous study implicated alveolar macrophages in the adaptive response. However, a complete characterization of the changes in all the macrophage subsets during adaptation have not been fully characterized. The aim of this study was to investigate the effects of single versus repeated chlorine exposure on alveolar, interstitial and bone marrow-derived macrophages. Methods: Wild-type (WT) BALB/c mice (8-12 weeks old) were exposed to 100 ppm chlorine for 5 minutes, either once or three times at 3 day intervals. Airway responsiveness to inhaled aerosols of methacholine (MCh) was assessed using the flexiVent, and lungs were lavaged or harvested and digested 24 hours post-exposure for analysis by flow cytometry. A control group was exposed to air and assessed similarly. Results: A single exposure to chlorine increased responsiveness to methacholine (AHR) and BAL fluid neutrophilic inflammation. Following three exposures, mice demonstrated adaptation, evidenced by a return of responsiveness to MCh to levels comparable to the air-exposed control group. There was also a marked reduction in BAL fluid neutrophil count, confirmed by flow cytometry showing reduced lung neutrophilia in the three times exposed group. Furthermore, there was a significant upregulation of heme oxygenase (HO)-1 expression in monocyte-derived macrophages and interstitial macrophages in the single-exposure group compared to the other groups, indicating significant oxidative stress but expression of HO-1 was restored to control levels after three exposures to chlorine. Additionally, arginase-1 expression was elevated in all macrophage phenotypes in the three times exposed group relative to the single exposure group, indicating a phenotype switch to the reparative M2 macrophages. Conclusions: The findings demonstrate that repeated chlorine exposure induces an adaptive response, improving respiratory function and inflammation. This adaptation is associated with alterations in all macrophage subsets, underscoring their potential role in protecting against airway inflammation from chlorine exposure.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.335
Teacher spread0.312 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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