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* Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
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 PGD2, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grants HL068669, AI068084, and P50-DE016191.
2 Address correspondence and reprint requests to Dr. Bruce D. Levy, Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail address: blevy{at}partners.org
3 Abbreviations used in this paper: EOS, eosinophil; Lymph, lymphocyte; CysLT, cysteinyl leukotriene; LX, lipoxin; DHA, docosahexaenoic acid; PD1, protectin D1; BAL, bronchoalveolar lavage; BALF, BAL fluid; LC, liquid chromatography; MS, mass spectrometry; EBC, exhaled breath condensate; PMN, neutrophil.
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