Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation
Acute respiratory inflammation, most commonly resulting from bacterial or viral infection, is one of the leading causes of death and disability worldwide. The inflammatory lipid mediator prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) and its rate-limiting enzyme, hematopoietic...
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| Autores principales: | , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/e9e36f38b12b402baa50c259a38526ee |
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| Sumario: | Acute respiratory inflammation, most commonly resulting from bacterial or viral infection, is one of the leading causes of death and disability worldwide. The inflammatory lipid mediator prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) and its rate-limiting enzyme, hematopoietic PGD synthase (hPGDS), are well-known drivers of allergic pulmonary inflammation. Here, we sought to investigate the source and role of hPGDS-derived PGD<sub>2</sub> in acute pulmonary inflammation. Murine bronchoalveolar monocytes/macrophages from LPS- but not OVA-induced lung inflammation released significant amounts of PGD<sub>2</sub>. Accordingly, human monocyte-derived macrophages expressed high basal levels of hPGDS and released significant levels of PGD<sub>2</sub> after LPS/IFN-γ, but not IL-4 stimulation. Human peripheral blood monocytes secreted significantly more PGD<sub>2</sub> than monocyte-derived macrophages. Using human precision-cut lung slices (PCLS), we observed that LPS/IFN-γ but not IL-4/IL-13 drive PGD<sub>2</sub> production in the lung. HPGDS inhibition prevented LPS-induced PGD<sub>2</sub> release by human monocyte-derived macrophages and PCLS. As a result of hPGDS inhibition, less TNF-α, IL-6 and IL-10 could be determined in PCLS-conditioned medium. Collectively, this dataset reflects the time-dependent release of PGD<sub>2</sub> by human phagocytes, highlights the importance of monocytes and macrophages as PGD<sub>2</sub> sources and suggests that hPGDS inhibition might be a potential therapeutic option for acute, non-allergic lung inflammation. |
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