title: Protective actions of aspirin-triggered (17R) resolvin D1 and its analogue, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester, in C5a-dependent IgG immune complex-induced inflammation and lung injury.
abstract: Increasing evidence suggests that the novel anti-inflammatory and proresolving mediators such as the resolvins play an important role during inflammation. However, the functions of these lipid mediators in immune complex-induced lung injury remain unknown. In this study, we determined the role of aspirin-triggered resolvin D1 (AT-RvD1) and its metabolically stable analog, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester (p-RvD1), in IgG immune complex-induced inflammatory responses in myeloid cells and injury in the lung. We show that lung vascular permeability in the AT-RvD1- or p-RvD1-treated mice was significantly reduced when compared with values in mice receiving control vesicle during the injury. Furthermore, i.v. administration of either AT-RvD1 or p-RvD1 caused significant decreases in the bronchoalveolar lavage fluid contents of neutrophils, inflammatory cytokines, and chemokines. Of interest, AT-RvD1 or p-RvD1 significantly reduced bronchoalveolar lavage fluid complement C5a level. By EMSA, we demonstrate that IgG immune complex-induced activation of NF-κB and C/EBPβ transcription factors in the lung was significantly inhibited by AT-RvD1 and p-RvD1. Moreover, AT-RvD1 dramatically mitigates IgG immune complex-induced NF-κB and C/EBP activity in alveolar macrophages. Also, secretion of TNF-α, IL-6, keratinocyte cell-derived chemokine, and MIP-1α from IgG immune complex-stimulated alveolar macrophages or neutrophils was significantly decreased by AT-RvD1. These results suggest a new approach to the blocking of immune complex-induced inflammation.
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; Zhejiang Respiratory Drugs Research Laboratory of the State Food and Drug Administration of China, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China;
authors.forename: Huifang
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; hgao@zeus.bwh.harvard.edu cnserhan@zeus.bwh.harvard.edu.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; hgao@zeus.bwh.harvard.edu cnserhan@zeus.bwh.harvard.edu.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001241:Aspirin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D022762:CCAAT-Enhancer-Binding Proteins / Q000276:immunology; D002460:Cell Line; D054405:Chemokine CCL3 / Q000276:immunology; D015936:Complement C5a / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004281:Docosahexaenoic Acids; D007074:Immunoglobulin G / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000936:Antigen-Antibody Complex; D022762:CCAAT-Enhancer-Binding Proteins; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D016207:Cytokines; D007074:Immunoglobulin G; D016328:NF-kappa B; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D015936:Complement C5a; D001241:Aspirin