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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 474498.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Acute lung injury is reduced in fat-1 mice endogenously synthesizing n-3 fatty acids
Authors:Mayer, K.; Kiessling, A.; Ott, J.; Schaefer, M. B.; Hecker, M.; Henneke, I.; Schulz, R.; Gunther, A.; Wang, J.; Wu, L.; Roth, J.; Seeger, W.; Kang, J. X.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Am J Respir Crit Care Med
Issue / Number:6
Start Page:474
End Page:83
Audience:Not Specified
Abstract / Description:RATIONALE: Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency. OBJECTIVES: To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI. METHODS: We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice--markers of sickness behavior--were also recorded. MEASUREMENTS AND MAIN RESULTS: In ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B(2) levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster. CONCLUSIONS: fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI.
Free Keywords:Acute Lung Injury/*metabolism/*prevention & control; Animals; Arachidonic Acid/metabolism; Behavior, Animal; Body Temperature; Bronchoalveolar Lavage Fluid/chemistry; Caenorhabditis elegans Proteins/genetics/metabolism; Chemokine CXCL2/analysis; Disease Models, Animal; Docosahexaenoic Acids/metabolism; Eicosapentaenoic Acid/*metabolism; Fat Emulsions, Intravenous/pharmacology; Fatty Acid Desaturases/genetics/metabolism; Fish Oils/pharmacology; Leukocyte Count; Leukocytes/pathology; Lung/metabolism/pathology; Mice; Mice, Transgenic; Motor Activity; NF-kappa B/metabolism; Respiration, Artificial; Thromboxane B2/analysis; Tumor Necrosis Factor-alpha/metabolism
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:University of Giessen Lung Center (UGLC), Medical Clinic II, Justus-Liebig-University Giessen, Klinikstr. 36, D-35392 Giessen, Germany. konstantin.mayer@uglc.de.
Identifiers:ISSN:1535-4970 (Electronic) 1073-449X (Linking)
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