Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent
| Autor: | Charles N. Serhan, Nan Chiang, Jesmond Dalli, Sarah K. Orr, Romain A. Colas |
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| Rok vydání: | 2015 |
| Předmět: |
Pulmonary and Respiratory Medicine
Docosahexaenoic Acids Physiology Peritonitis Biology Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Phagocytosis Physiology (medical) Escherichia coli Animals Humans Lung Cells Cultured Escherichia coli Infections 030304 developmental biology Inflammation Phagocytes 0303 health sciences Macrophages Zymosan Esters Cell Biology Resolvin d1 3. Good health Neutrophil Infiltration Reperfusion Injury Immunology Call for Papers Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 308:L904-L911 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17 R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 μg) reduced neutrophil infiltration into the lungs by 58 ± 9% and was significantly more potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by ∼57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at picomolar concentrations (10−12 M) stimulated phagocytosis of zymosan A particles. BDA-RvD1 activated human recombinant G protein-coupled receptor 32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares defining proresolving actions of RvD1, including inhibiting leukocyte infiltration and stimulating phagocytosis. Moreover, they provide evidence for a new analog mimetic and example of an immunoresolvent, namely an agent that stimulates active resolution of inflammation, for a potential new therapeutic class. |
| Databáze: | OpenAIRE |
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