Abstract
Inhalation of particles results in pulmonary inflammation; however, treatments are currently lacking. Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid shown to exhibit anti-inflammatory capabilities. The impact of DHA on particle-induced inflammation is unclear; therefore, the aim of this study was to examine the hypothesis that DHA downregulates macrophage inflammatory responses by altering phagolysosomal membrane permeability (LMP) and shifting macrophage phenotype. Isolated Balb/c alveolar macrophages (AM) were polarized into M1, M2a, M2b, or M2c phenotypes in vitro, treated with DHA, and exposed to a multi-walled carbon nanotube (MWNCT) or crystalline silica (SiO2). Results showed minimal cytotoxicity, robust effects for silica particle uptake, and LMP differences between phenotypes. Docosahexaenoic acid prevented these effects to the greatest extent in M2c phenotype. To determine if DHA affected inflammation similarly in vivo, Balb/c mice were placed on a control or 1% DHA diet for 3 weeks, instilled with the same particles, and assessed 24 hr following instillation. Data demonstrated that in contrast to in vitro findings, DHA increased pulmonary inflammation and LMP. These results suggest that pulmonary responses in vivo may not necessarily be predicted from single-cell responses in vitro.
| Original language | English |
|---|---|
| Pages (from-to) | 152-172 |
| Number of pages | 21 |
| Journal | Journal of Toxicology and Environmental Health - Part A: Current Issues |
| Volume | 84 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2021 |
Funding
This work was supported by the National Institute of Environmental Health Sciences [F31 ES028100, R01 ES023209, R01 ES027353]; National Institute of General Medical Sciences [P30 GM103338]. Paige Fletcher was supported by the Ruth L. Kirschstein NRSA Pre-doctoral Fellowship from the National Institute of Environmental Health Sciences under F31 ES028100. This research was supported by the National Institute of Environmental Health Sciences under Grants R01 ES023209 and R01 ES027353 and by the National Institute of General Medical Sciences under Grant P30 GM103338. The content within is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Paige Fletcher was awarded one of QIAGEN’s featured young scientists of the month (November 2018) where she received QIAGEN products that contributed to this research. The authors would like to thank the technical support from the CEHS Core Facilities: Inhalation and Pulmonary Physiology Core, Molecular Histology and Fluorescence Imaging Core, and the Fluorescence Cytometry Core. A special thank you to: Dr. Joanna Kreitinger at Dermaxon and Dr. Sarjubhai Patel at FYR Diagnostics for use of their 384-well CFX Maestro’s; Britten Postma, Mary Buford, Lou Herritt, and Pam Shaw within the CEHS Core facilities; UM’s Laboratory Animal Resources technicians and facility; and Iheanyi Amadi for help with lung airway thickness analysis. Paige Fletcher was supported by the Ruth L. Kirschstein NRSA Pre-doctoral Fellowship from the National Institute of Environmental Health Sciences under F31 ES028100. This research was supported by the National Institute of Environmental Health Sciences under Grants R01 ES023209 and R01 ES027353 and by the National Institute of General Medical Sciences under Grant P30 GM103338. The content within is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Paige Fletcher was awarded one of QIAGEN’s featured young scientists of the month (November 2018) where she received QIAGEN products that contributed to this research. The authors would like to thank the technical support from the CEHS Core Facilities: Inhalation and Pulmonary Physiology Core, Molecular Histology and Fluorescence Imaging Core, and the Fluorescence Cytometry Core. A special thank you to: Dr. Joanna Kreitinger at Dermaxon and Dr. Sarjubhai Patel at FYR Diagnostics for use of their 384-well CFX Maestro’s; Britten Postma, Mary Buford, Lou Herritt, and Pam Shaw within the CEHS Core facilities; UM’s Laboratory Animal Resources technicians and facility; and Iheanyi Amadi for help with lung airway thickness analysis.
| Funder number |
|---|
| P30 GM103338 |
| R01 ES027353, F31 ES028100, R01ES023209 |
Keywords
- Pulmonary inflammation
- crystalline silica
- macrophage phenotype
- multi-walled carbon nanotube
- phagolysosomal membrane damage