Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity
Abstract Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-017-02538-5 |
| _version_ | 1797669596216426496 |
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| author | Oliver Werz Jana Gerstmeier Stephania Libreros Xavier De la Rosa Markus Werner Paul C. Norris Nan Chiang Charles N. Serhan |
| author_facet | Oliver Werz Jana Gerstmeier Stephania Libreros Xavier De la Rosa Markus Werner Paul C. Norris Nan Chiang Charles N. Serhan |
| author_sort | Oliver Werz |
| collection | DOAJ |
| description | Abstract Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1. E. coli activates M2 macrophages to translocate 5-LOX and 15-LOX-1 to different subcellular locales in a Ca2+-dependent manner. Neither attenuated nor non-pathogenic E. coli mobilize Ca2+ or activate LOXs, rather these bacteria stimulate prostaglandin production. RvD5 is more potent than leukotriene B4 at enhancing macrophage phagocytosis. These results indicate that M1 and M2 macrophages respond to pathogenic bacteria differently, producing either leukotrienes or resolvins that further distinguish inflammatory or pro-resolving phenotypes. |
| first_indexed | 2024-03-11T20:46:44Z |
| format | Article |
| id | doaj.art-bf8ddff4771343aba2fa655e1c5cf782 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T20:46:44Z |
| publishDate | 2018-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-bf8ddff4771343aba2fa655e1c5cf7822023-10-01T11:22:00ZengNature PortfolioNature Communications2041-17232018-01-019111210.1038/s41467-017-02538-5Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicityOliver Werz0Jana Gerstmeier1Stephania Libreros2Xavier De la Rosa3Markus Werner4Paul C. Norris5Nan Chiang6Charles N. Serhan7Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University JenaCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University JenaCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolAbstract Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1. E. coli activates M2 macrophages to translocate 5-LOX and 15-LOX-1 to different subcellular locales in a Ca2+-dependent manner. Neither attenuated nor non-pathogenic E. coli mobilize Ca2+ or activate LOXs, rather these bacteria stimulate prostaglandin production. RvD5 is more potent than leukotriene B4 at enhancing macrophage phagocytosis. These results indicate that M1 and M2 macrophages respond to pathogenic bacteria differently, producing either leukotrienes or resolvins that further distinguish inflammatory or pro-resolving phenotypes.https://doi.org/10.1038/s41467-017-02538-5 |
| spellingShingle | Oliver Werz Jana Gerstmeier Stephania Libreros Xavier De la Rosa Markus Werner Paul C. Norris Nan Chiang Charles N. Serhan Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity Nature Communications |
| title | Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| title_full | Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| title_fullStr | Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| title_full_unstemmed | Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| title_short | Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| title_sort | human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity |
| url | https://doi.org/10.1038/s41467-017-02538-5 |
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