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: 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
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Publicado: MDPI AG 2021
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic 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
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