Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi
Summary: Neutrophil swarming is an emergent host defense mechanism triggered by targets larger than a single neutrophil’s capacity to phagocytose. Swarming synergizes neutrophil functions, including chemotaxis, phagocytosis, and reactive oxygen species (ROS) production, and coordinates their deploym...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222014985 |
| _version_ | 1811240868631281664 |
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| author | Alex Hopke Tian Lin Allison K. Scherer Ashley E. Shay Kyle D. Timmer Brittany Wilson-Mifsud Michael K. Mansour Charles N. Serhan Daniel Irimia Bryan P. Hurley |
| author_facet | Alex Hopke Tian Lin Allison K. Scherer Ashley E. Shay Kyle D. Timmer Brittany Wilson-Mifsud Michael K. Mansour Charles N. Serhan Daniel Irimia Bryan P. Hurley |
| author_sort | Alex Hopke |
| collection | DOAJ |
| description | Summary: Neutrophil swarming is an emergent host defense mechanism triggered by targets larger than a single neutrophil’s capacity to phagocytose. Swarming synergizes neutrophil functions, including chemotaxis, phagocytosis, and reactive oxygen species (ROS) production, and coordinates their deployment by many interacting neutrophils. The potent inflammatory lipid mediator leukotriene B4 (LTB4) has been established as central to orchestrating neutrophil activities during swarming. However, the details regarding how this eicosanoid choreographs the neutrophils involved in swarming are not well explained. Here we leverage microfluidics, genetically deficient mouse cells, and targeted metabolipidomic analysis to demonstrate that transcellular biosynthesis occurs among neutrophils to generate LTB4. Furthermore, transcellular biosynthesis is an entirely sufficient means of generating LTB4 for the purposes of orchestrating neutrophil swarming. These results further our understanding of how neutrophils coordinate their activities during swarming, which will be critical in the design of eventual therapies that can harness the power of swarming behavior. |
| first_indexed | 2024-04-12T13:27:28Z |
| format | Article |
| id | doaj.art-9702e75d772246ab84e3c19a0369c655 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T13:27:28Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9702e75d772246ab84e3c19a0369c6552022-12-22T03:31:17ZengElsevieriScience2589-00422022-10-012510105226Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungiAlex Hopke0Tian Lin1Allison K. Scherer2Ashley E. Shay3Kyle D. Timmer4Brittany Wilson-Mifsud5Michael K. Mansour6Charles N. Serhan7Daniel Irimia8Bryan P. Hurley9Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Shriners Hospital for Children, Boston, MA 02114, USAHarvard Medical School, Boston, MA 02115, USA; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USAHarvard Medical School, Boston, MA 02115, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USAHarvard Medical School, Boston, MA 02115, USA; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USAMucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USAHarvard Medical School, Boston, MA 02115, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USAHarvard Medical School, Boston, MA 02115, USA; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USACenter for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Shriners Hospital for Children, Boston, MA 02114, USA; Corresponding authorHarvard Medical School, Boston, MA 02115, USA; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Corresponding authorSummary: Neutrophil swarming is an emergent host defense mechanism triggered by targets larger than a single neutrophil’s capacity to phagocytose. Swarming synergizes neutrophil functions, including chemotaxis, phagocytosis, and reactive oxygen species (ROS) production, and coordinates their deployment by many interacting neutrophils. The potent inflammatory lipid mediator leukotriene B4 (LTB4) has been established as central to orchestrating neutrophil activities during swarming. However, the details regarding how this eicosanoid choreographs the neutrophils involved in swarming are not well explained. Here we leverage microfluidics, genetically deficient mouse cells, and targeted metabolipidomic analysis to demonstrate that transcellular biosynthesis occurs among neutrophils to generate LTB4. Furthermore, transcellular biosynthesis is an entirely sufficient means of generating LTB4 for the purposes of orchestrating neutrophil swarming. These results further our understanding of how neutrophils coordinate their activities during swarming, which will be critical in the design of eventual therapies that can harness the power of swarming behavior.http://www.sciencedirect.com/science/article/pii/S2589004222014985ImmunologyCell biology |
| spellingShingle | Alex Hopke Tian Lin Allison K. Scherer Ashley E. Shay Kyle D. Timmer Brittany Wilson-Mifsud Michael K. Mansour Charles N. Serhan Daniel Irimia Bryan P. Hurley Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi iScience Immunology Cell biology |
| title | Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi |
| title_full | Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi |
| title_fullStr | Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi |
| title_full_unstemmed | Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi |
| title_short | Transcellular biosynthesis of leukotriene B4 orchestrates neutrophil swarming to fungi |
| title_sort | transcellular biosynthesis of leukotriene b4 orchestrates neutrophil swarming to fungi |
| topic | Immunology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222014985 |
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