Endocytosis of particulate matter induces cytokine production by neutrophil via Toll-like receptor 4
Abstract
Particulate matter (PM) with a median diameter <2.5 μm, is associated with respiratory and cardiovascular diseases. We previously reported the biological effects of PM in vivo, and although neutrophils play an important role in initiating inflammation, few reports have focused on the relationship between PM inhalation and immune responses. Here, we investigated the effect of PM particle size on neutrophils, including their endocytosis activity and reactive oxygen species (ROS) production. Flow cytometry analysis indicated that 1 μm particles are readily endocytosed by neutrophils and that endocytosis is reduced at 4 °C. Inhibitors of the pleckstrin homology domain of dynamin repressed this process; however, GTPase and clathrin inhibitors did not affect endocytosis. Endocytosis by neutrophils in Toll-like receptor 4 (TLR4)- and MyD88-knockout mice was reduced compared with that in wild-type mice, indicating that TLR4 and MyD88 are important for the process. Neutrophil-mediated endocytosis caused oxidative stress, and N-acetylcysteine enhanced endocytosis. Expression levels of the oxidative stress markers, heme oxygenase-1 and p62 protein, were increased in an endocytosis-dependent manner. Phagocytosed neutrophils produced IL-6 and TNFα, whose production was decreased by dynamin inhibitors. We observed that infiltrated CD11b-positive cells in bronchoalveolar lavage fluid endocytose PMs. Overall, these results indicate that endocytosis and ROS production via TLR4 are important for the initiation of immune responses by neutrophils.
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PM2.5 induces the recruitment of neutrophils.
“Previous studies reported that PM2.5 induces the recruitment of neutrophils (52, 53), which produces TNF-α (54).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [52]
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- Authors
- Miyake, T., Wang, D., Matsuoka, H., Morita, K., Yasuda, H., Yatera, K., Kanazawa, T., & Yoshida, Y.
- Affiliations
- University of Occupational and Environmental Health Japan (JP)
- Corresponding author
- Yoshida, Yasuhiro
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 57
- Pages
- 190-199
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W2789450718
- Cited by
- 20
- References
- 33
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-08-01)
- Open access
- closed
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23510070)
- The Science Research Promotion Fund (24390159)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- particulate matter, neutrophils, endocytosis, TLR4, MyD88, reactive oxygen species, oxidative stress, heme oxygenase-1, p62, interleukin-6, TNF-α, dynamin, particle size, air pollution, inflammation, bronchoalveolar lavage
- MeSH terms
- Animals, Cells, Cultured, Endocytosis, Membrane Proteins, Mice, Inbred BALB C, Neutrophils, Particle Size, Tumor Necrosis Factor-alpha, Interleukin-6, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Dynamins, Toll-Like Receptor 4, Mice, Heme Oxygenase-1, Particulate Matter, Myeloid Differentiation Factor 88
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