Effect of structural modification at carbon atom 1 of leukotriene B4 on the chemotactic and metabolic response of human neutrophils |
| |
| Authors: | R M Clancy C A Dahinden T E Hugli |
| |
| Institution: | 1. Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Ghent, Belgium;2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;3. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK;4. Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research, Ghent, Belgium;5. Molecular and Cellular Oncology Lab, VIB-UGent Center for Inflammation Research, Ghent, Belgium;6. Laboratory of Mucosal Immunology and Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium;7. Department of Respiratory Medicine, Ghent University, Ghent, Belgium;8. Laboratory of Molecular Signaling and Cell Death, VIB-UGent Center for Inflammation Research, Ghent, Belgium;9. Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS 13288 Marseille, France;10. MRC Centre for Inflammation Research, University of Edinburgh, The Queen''s Medical Research Institute, UK;11. Mater Research-University of Queensland, Translational Research Institute, Qld 4102, Australia;12. Myeloid Cell Immunology Lab, VIB-UGent Center for Inflammation Research, Brussels, Belgium;13. Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium;14. Centre d’Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France;15. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium;1. Department of Plant Biology and Genome Center, University of California, Davis, Davis, CA 95616, USA;2. Plant Ecophysiology, Institute of Environmental Biology, Utrecht University, 3584 Utrecht, the Netherlands;3. Plant Biology Graduate Group, University of California, Davis, Davis, CA 95616, USA;4. Integrative Genetics and Genomics Graduate Group, University of California, Davis, Davis, CA 95616, USA;5. Center for Plant Cell Biology, Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA 92521, USA;6. IBBM, FCE-UNLP CONICET, La Plata 1900, Argentina;7. Department of Cell and Systems Biology/Centre for the Analysis of Genome Evolution and Function, University of Toronto, 25 Willcocks St., Toronto, ON M5S 3B2, Canada;8. Department of Plant Biology, University of California, Davis, Davis, CA 95616, USA;9. Fort Valley State University, Fort Valley, GA 31030, USA;10. Department of Biomedical Engineering and Genome Center, University of California, Davis, Davis, CA 95616, USA;11. Department of Biology, Emory University, Atlanta, GA 30322, USA;12. Department of Biology, University of Padova, Padova, Italy;13. Department of Plant Sciences, University of California, Davis, Davis, CA 95616, USA;14. Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1432 Ås, Norway;1. CETT Barcelona School of Tourism, Hospitality and Gastronomy, University of Barcelona, Av. Can Marcet, 36-38, 08035, Barcelona, Spain;2. Institute of Agrifood Research and Technology (IRTA), Postharvest Programme, Edifici Fruitcenter, Parc Científic i Tecnològic Agroalimentari de Lleida, 25003, Lleida, Spain;1. Institute of Applied Computer Science, Lodz University of Technology, Stefanowskiego 18/22, 90-924 Lodz, Poland;2. Department of Plant Physiology and Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland;1. State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai''an, Shandong, 271018, China;2. College of Agriculture and Bioengineering, Heze University, Heze, Shandong, 274015, China |
| |
| Abstract: | Human neutrophils biosynthesize the chemoattractant leukotriene B4 (LTB4) and metabolize LTB4 to omega oxidative products 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4). In this study, we prepared the C-1 methyl ester and N-methyl amide of LTB4 and then examined neutrophil chemotaxis and metabolism of these derivatives of LTB4. The results show that chemical modification of LTB4 at carbon atom 1 dramatically affects metabolism of the lipid molecule. The free acid form of LTB4 was taken up and metabolized by human neutrophils, while the methyl ester and N-methyl amide derivatives were poor substrates for omega oxidation. Although human neutrophils were poorly attracted to the methyl ester of LTB4, the amide derivative was a complete agonist of the neutrophil chemotactic response and displayed an ED50 for chemotaxis identical to that of LTB4. Therefore, we concluded that omega oxidation is not a requirement for the neutrophil chemotactic response induced by LTB4. These results also indicate that the N-methyl amide of LTB4 may be a useful ligand for the elucidation of molecular mechanisms operative in neutrophil chemotaxis to LTB4, since the C-1 derivative is not further metabolized. Two separate responses of human neutrophils are elicited by LTB4, resulting in both cellular activation and generation of omega oxidation products. It appears that putative receptors on the neutrophils can distinguish between LTB4 and certain derivatives that are structurally identical except for modification at the C-1 position (i.e., the methyl ester). LTB4 derivatives modified at the C-1 position do not undergo conversion to omega oxidation products by the neutrophil. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
