Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation: To Resolve or Not?
Top Cited Papers
- 31 October 2010
- journal article
- review article
- Published by Elsevier BV in The American Journal of Pathology
- Vol. 177 (4), 1576-1591
- https://doi.org/10.2353/ajpath.2010.100322
Abstract
Because inflammation is appreciated as a unifying basis of many widely occurring diseases, the mechanisms involved in its natural resolution are of considerable interest. Using contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived mediators and pathways were uncovered in the resolution of inflammatory exudates. These new families of local mediators control both the duration and magnitude of acute inflammation as well as the return of the site to homeostasis in the process of catabasis. This new genus of specialized proresolving mediators (SPM) includes essential fatty acid-derived lipoxins, resolvins, protectins, and, most recently, maresins. These families were named based on their unique structures and potent stereoselective actions. The temporally initiated biosynthesis of SPM and their direct impact on leukocyte trafficking and macrophage-directed clearance mechanisms provide clear evidence that resolution is an active, programmed response at the tissue level. Moreover, SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance macrophage uptake and clearance of apoptotic PMN and microbial particles) actions as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation and proresolution are different responses of the host and novel defining properties of these molecules. The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies.Keywords
Funding Information
- National Institutes of Health (GM038765, DK074448, DE019938)
This publication has 147 references indexed in Scilit:
- Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgeryProstaglandins, Leukotrienes & Essential Fatty Acids, 2010
- The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and HumansCell, 2010
- Neuroprotectin D1/protectin D1 stereoselective and specific binding with human retinal pigment epithelial cells and neutrophilsProstaglandins, Leukotrienes & Essential Fatty Acids, 2010
- Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium–induced colitisInflammatory Bowel Diseases, 2010
- Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsisNature, 2009
- The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory moleculesNature Immunology, 2009
- Polyunsaturated fatty acids and inflammatory processes: New twists in an old taleBiochimie, 2009
- Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammationNature Immunology, 2008
- Resolvin E1 and protectin D1 activate inflammation-resolution programmesNature, 2007
- Resolution of inflammation: the beginning programs the endNature Immunology, 2005