title: Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness.
abstract: Protectins are newly identified natural chemical mediators that counter leukocyte activation to promote resolution of inflammation. In this study, we provide the first evidence for protectin D1 (PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) formation from docosahexaenoic acid in human asthma in vivo and PD1 counterregulatory actions in allergic airway inflammation. PD1 and 17S-hydroxy-docosahexaenoic acid were present in exhaled breath condensates from healthy subjects. Of interest, levels of PD1 were significantly lower in exhaled breath condensates from subjects with asthma exacerbations. PD1 was also present in extracts of murine lungs from both control animals and those sensitized and aerosol challenged with allergen. When PD1 was administered before aeroallergen challenge, airway eosinophil and T lymphocyte recruitment were decreased, as were airway mucus, levels of specific proinflammatory mediators, including IL-13, cysteinyl leukotrienes, and PGD(2), and airway hyperresponsiveness to inhaled methacholine. Of interest, PD1 treatment after aeroallergen challenge markedly accelerated the resolution of airway inflammation. Together, these findings provide evidence for endogenous PD1 as a pivotal counterregulatory signal in allergic airway inflammation and point to new therapeutic strategies for modulating inflammation in asthmatic lung.
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. blevy@partners.org
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.forename: Katherine
authors.initials: K
authors.lastname: Gotlinger
authors.forename: Oliver
authors.initials: O
authors.lastname: Haworth
authors.forename: Song
authors.initials: S
authors.lastname: Hong
authors.forename: Shamsah
authors.initials: S
authors.lastname: Kazani
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Haley
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: C487679:protectin D1; D004281:Docosahexaenoic Acids; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid