Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells
Leukotriene B4 (LTB4) biosynthesis by polymorphonuclear leukocytes (PMNs) is an important factor of inflammatory responses. PMNs also release LTA4, an unstable intermediate that can be taken up by neighboring cells and metabolized into LTC4. Most studies of LT synthesis have been carried out using h...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-03-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752043247X |
| _version_ | 1818731725052706816 |
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| author | Miguel A. Gijón Simona Zarini Robert C. Murphy |
| author_facet | Miguel A. Gijón Simona Zarini Robert C. Murphy |
| author_sort | Miguel A. Gijón |
| collection | DOAJ |
| description | Leukotriene B4 (LTB4) biosynthesis by polymorphonuclear leukocytes (PMNs) is an important factor of inflammatory responses. PMNs also release LTA4, an unstable intermediate that can be taken up by neighboring cells and metabolized into LTC4. Most studies of LT synthesis have been carried out using human PMNs, but very little information is available about mouse PMNs. Mouse bone marrow PMNs were found to synthesize eicosanoids upon stimulation with A23187, fMLP, or zymosan. The major eicosanoids produced are LTB4 and 5-hydroxyeicosatetraenoic acid, with some nonenzymatic products of LTA4 hydrolysis. No cysteinyl leukotrienes were produced, in contrast to what was observed with human blood neutrophil preparations. Human megakaryoblast-like MEG-01 cells synthesized thromboxane B2 and prostaglandin E2 in response to A23187 but produced no 5-lipoxygenase (5-LO)-derived eicosanoids. When mouse bone marrow cells (mBMCs) and MEG-01 cells were stimulated during coincubation, LTC4 and LTD4 were produced. Mouse peritoneal macrophages from 5-LO-deficient mice were able to synthesize LTC4 when incubated with mBMCs from wild-type mice, demonstrating transcellular exchange of LTA4 from mBMCs into murine peritoneal macrophages. These data demonstrate that murine bone marrow PMNs are a valid model for the study of LT biosynthesis, which now offers the possibility to investigate specific biochemical pathways through the use of transgenic mice. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:22:14Z |
| publishDate | 2007-03-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-479890c69d7440fd9bc0772762e451a22022-12-21T21:28:51ZengElsevierJournal of Lipid Research0022-22752007-03-01483716725Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cellsMiguel A. Gijón0Simona Zarini1Robert C. Murphy2Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045-6511Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045-6511Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045-6511Leukotriene B4 (LTB4) biosynthesis by polymorphonuclear leukocytes (PMNs) is an important factor of inflammatory responses. PMNs also release LTA4, an unstable intermediate that can be taken up by neighboring cells and metabolized into LTC4. Most studies of LT synthesis have been carried out using human PMNs, but very little information is available about mouse PMNs. Mouse bone marrow PMNs were found to synthesize eicosanoids upon stimulation with A23187, fMLP, or zymosan. The major eicosanoids produced are LTB4 and 5-hydroxyeicosatetraenoic acid, with some nonenzymatic products of LTA4 hydrolysis. No cysteinyl leukotrienes were produced, in contrast to what was observed with human blood neutrophil preparations. Human megakaryoblast-like MEG-01 cells synthesized thromboxane B2 and prostaglandin E2 in response to A23187 but produced no 5-lipoxygenase (5-LO)-derived eicosanoids. When mouse bone marrow cells (mBMCs) and MEG-01 cells were stimulated during coincubation, LTC4 and LTD4 were produced. Mouse peritoneal macrophages from 5-LO-deficient mice were able to synthesize LTC4 when incubated with mBMCs from wild-type mice, demonstrating transcellular exchange of LTA4 from mBMCs into murine peritoneal macrophages. These data demonstrate that murine bone marrow PMNs are a valid model for the study of LT biosynthesis, which now offers the possibility to investigate specific biochemical pathways through the use of transgenic mice.http://www.sciencedirect.com/science/article/pii/S002222752043247Xmurine neutrophilsleukotriene B4leukotriene C4MEG-01 cellsmass spectrometry |
| spellingShingle | Miguel A. Gijón Simona Zarini Robert C. Murphy Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells Journal of Lipid Research murine neutrophils leukotriene B4 leukotriene C4 MEG-01 cells mass spectrometry |
| title | Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| title_full | Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| title_fullStr | Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| title_full_unstemmed | Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| title_short | Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| title_sort | biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in murine bone marrow cells |
| topic | murine neutrophils leukotriene B4 leukotriene C4 MEG-01 cells mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S002222752043247X |
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