PMID- 34769126 OWN - NLM STAT- MEDLINE DCOM- 20211221 LR - 20230607 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 21 DP - 2021 Oct 28 TI - Monocytes and Macrophages Serve as Potent Prostaglandin D(2) Sources during Acute, Non-Allergic Pulmonary Inflammation. LID - 10.3390/ijms222111697 [doi] LID - 11697 AB - 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(2) (PGD(2)) 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(2) in acute pulmonary inflammation. Murine bronchoalveolar monocytes/macrophages from LPS- but not OVA-induced lung inflammation released significant amounts of PGD(2). Accordingly, human monocyte-derived macrophages expressed high basal levels of hPGDS and released significant levels of PGD(2) after LPS/IFN-gamma, but not IL-4 stimulation. Human peripheral blood monocytes secreted significantly more PGD(2) than monocyte-derived macrophages. Using human precision-cut lung slices (PCLS), we observed that LPS/IFN-gamma but not IL-4/IL-13 drive PGD(2) production in the lung. HPGDS inhibition prevented LPS-induced PGD(2) release by human monocyte-derived macrophages and PCLS. As a result of hPGDS inhibition, less TNF-alpha, IL-6 and IL-10 could be determined in PCLS-conditioned medium. Collectively, this dataset reflects the time-dependent release of PGD(2) by human phagocytes, highlights the importance of monocytes and macrophages as PGD(2) sources and suggests that hPGDS inhibition might be a potential therapeutic option for acute, non-allergic lung inflammation. FAU - Rittchen, Sonja AU - Rittchen S AUID- ORCID: 0000-0002-8753-4384 AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. AD - Ludwig Boltzmann Institute for Lung Vascular Research, 8010 Graz, Austria. FAU - Jandl, Katharina AU - Jandl K AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. AD - Ludwig Boltzmann Institute for Lung Vascular Research, 8010 Graz, Austria. FAU - Lanz, Ilse AU - Lanz I AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. FAU - Reiter, Bernhard AU - Reiter B AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. FAU - Ferreiros, Nerea AU - Ferreiros N AD - Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany. FAU - Kratz, Daniel AU - Kratz D AD - Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany. FAU - Lindenmann, Jorg AU - Lindenmann J AUID- ORCID: 0000-0003-1276-7666 AD - Department of Surgery, Divison of Thoracic and Hyperbaric Surgery, Medical University of Graz, 8010 Graz, Austria. FAU - Brcic, Luka AU - Brcic L AUID- ORCID: 0000-0002-9098-8416 AD - Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria. FAU - Barnthaler, Thomas AU - Barnthaler T AUID- ORCID: 0000-0002-4988-3700 AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. FAU - Atallah, Reham AU - Atallah R AUID- ORCID: 0000-0001-7184-4882 AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. FAU - Olschewski, Horst AU - Olschewski H AUID- ORCID: 0000-0002-2834-7466 AD - Ludwig Boltzmann Institute for Lung Vascular Research, 8010 Graz, Austria. AD - Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, 8010 Graz, Austria. FAU - Sturm, Eva M AU - Sturm EM AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. FAU - Heinemann, Akos AU - Heinemann A AUID- ORCID: 0000-0002-8554-2372 AD - Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria. AD - BioTechMed, 8010 Graz, Austria. LA - eng GR - DOC 31/FWF_/Austrian Science Fund FWF/Austria PT - Journal Article DEP - 20211028 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Lipocalins) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.99.2 (prostaglandin R2 D-isomerase) RN - RXY07S6CZ2 (Prostaglandin D2) SB - IM MH - Acute Lung Injury/*immunology MH - Animals MH - Humans MH - Intramolecular Oxidoreductases/*metabolism MH - Lipocalins/*metabolism MH - Macrophages, Alveolar/*metabolism MH - Mice MH - Monocytes/*metabolism MH - Prostaglandin D2/*metabolism PMC - PMC8584273 OTO - NOTNLM OT - acute lung injury OT - hPGDS OT - lipopolysaccharide OT - mononuclear phagocytes OT - precision-cut lung slices OT - prostaglandin D2 COIS- The authors declare no conflict of interest. EDAT- 2021/11/14 06:00 MHDA- 2021/12/22 06:00 PMCR- 2021/10/28 CRDT- 2021/11/13 01:04 PHST- 2021/09/29 00:00 [received] PHST- 2021/10/20 00:00 [revised] PHST- 2021/10/25 00:00 [accepted] PHST- 2021/11/13 01:04 [entrez] PHST- 2021/11/14 06:00 [pubmed] PHST- 2021/12/22 06:00 [medline] PHST- 2021/10/28 00:00 [pmc-release] AID - ijms222111697 [pii] AID - ijms-22-11697 [pii] AID - 10.3390/ijms222111697 [doi] PST - epublish SO - Int J Mol Sci. 2021 Oct 28;22(21):11697. doi: 10.3390/ijms222111697.