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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oai:doaj.org-article:e9e36f38b12b402baa50c259a38526ee2021-11-11T17:09:27ZMonocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation10.3390/ijms2221116971422-00671661-6596https://doaj.org/article/e9e36f38b12b402baa50c259a38526ee2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11697https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Acute 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.Sonja RittchenKatharina JandlIlse LanzBernhard ReiterNerea FerreirósDaniel KratzJörg LindenmannLuka BrcicThomas BärnthalerReham AtallahHorst OlschewskiEva M. SturmAkos HeinemannMDPI AGarticleprostaglandin D<sub>2</sub>hPGDSlipopolysaccharideacute lung injurymononuclear phagocytesprecision-cut lung slicesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11697, p 11697 (2021) |
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prostaglandin D<sub>2</sub> hPGDS lipopolysaccharide acute lung injury mononuclear phagocytes precision-cut lung slices Biology (General) QH301-705.5 Chemistry QD1-999 |
spellingShingle |
prostaglandin D<sub>2</sub> hPGDS lipopolysaccharide acute lung injury mononuclear phagocytes precision-cut lung slices Biology (General) QH301-705.5 Chemistry QD1-999 Sonja Rittchen Katharina Jandl Ilse Lanz Bernhard Reiter Nerea Ferreirós Daniel Kratz Jörg Lindenmann Luka Brcic Thomas Bärnthaler Reham Atallah Horst Olschewski Eva M. Sturm Akos Heinemann Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
description |
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. |
format |
article |
author |
Sonja Rittchen Katharina Jandl Ilse Lanz Bernhard Reiter Nerea Ferreirós Daniel Kratz Jörg Lindenmann Luka Brcic Thomas Bärnthaler Reham Atallah Horst Olschewski Eva M. Sturm Akos Heinemann |
author_facet |
Sonja Rittchen Katharina Jandl Ilse Lanz Bernhard Reiter Nerea Ferreirós Daniel Kratz Jörg Lindenmann Luka Brcic Thomas Bärnthaler Reham Atallah Horst Olschewski Eva M. Sturm Akos Heinemann |
author_sort |
Sonja Rittchen |
title |
Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
title_short |
Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
title_full |
Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
title_fullStr |
Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
title_full_unstemmed |
Monocytes and Macrophages Serve as Potent Prostaglandin D<sub>2</sub> Sources during Acute, Non-Allergic Pulmonary Inflammation |
title_sort |
monocytes and macrophages serve as potent prostaglandin d<sub>2</sub> sources during acute, non-allergic pulmonary inflammation |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/e9e36f38b12b402baa50c259a38526ee |
work_keys_str_mv |
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