# The Role of Mast Cells in the Remodeling Effects of Molecular Hydrogen on the Lung Local Tissue Microenvironment under Simulated Pulmonary Hypertension.
> 肺高血圧モデルにおける分子状水素の肺局所組織微小環境リモデリングへのマスト細胞の関与


## Abstract

Using a rat model of monocrotaline (MCT)-induced pulmonary hypertension, this study examined how inhaled molecular hydrogen (H2) affects mast cells (MCs) and the fibrotic phenotype of the pulmonary local tissue microenvironment. MCT exposure markedly elevated intrapulmonary MC counts, increased tryptase-positive MCs with elevated TGF-β expression, enhanced MC interactions with macrophages, plasma cells, and fibroblasts, and promoted collagen fibrillogenesis along with expansion of extracellular matrix collagen and elastic fibers. Co-administration of H2 with MCT tended to reduce the intrapulmonary MC population and attenuate the fibrotic phenotype relative to MCT alone. Specifically, MC-associated collagen fibrillogenesis activity declined, TGF-β and tryptase expression in MCs decreased, and the absolute and relative content of reticular and elastic fibers in the lung stroma was reduced. These findings indicate that inhaled H2 exerts antifibrotic effects in the MCT-exposed rat lung through mechanisms involving MC modulation, revealing previously uncharacterized pathways by which H2 influences extracellular matrix remodeling under inflammatory conditions.

### Mechanism

Inhaled H2 suppresses TGF-β and tryptase expression in mast cells, reduces MC-associated collagen fibrillogenesis, and decreases reticular and elastic fiber accumulation in the lung stroma, thereby attenuating pulmonary fibrotic remodeling.

## Bibliographic

- **Authors**: Atiakshin D, Kostin A, Alekhnovich A, Volodkin A, Ignatyuk M, Klabukov I, et al.
- **Journal**: Int J Mol Sci
- **Year**: 2024 (2024-10-13)
- **PMID**: [39456794](https://pubmed.ncbi.nlm.nih.gov/39456794/)
- **DOI**: [10.3390/ijms252011010](https://doi.org/10.3390/ijms252011010)
- **PMC**: [PMC11507233](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507233/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 39456794. https://h2-papers.org/en/papers/39456794
> **Source**: PubMed PMID [39456794](https://pubmed.ncbi.nlm.nih.gov/39456794/)