title: Immunomodulation by n-3- versus n-6-rich lipid emulsions in murine acute lung injury--role of platelet-activating factor receptor.
abstract: OBJECTIVE
  Cytokines, platelet-activating factor (PAF), and eicosanoids control local and systemic inflammation. Conventional soybean oil-based lipid emulsions used for parenteral nutrition may aggravate the leukocyte inflammatory response or adhesion to the vessel wall. Fish oil-based lipid emulsions, in contrast, may exert an anti-inflammatory effect.
  
  
  METHODS
  We investigated the impact of lipid emulsions on leukocyte invasion, protein leakage, and cytokines in two murine models of acute inflammation.
  
  
  METHODS
  Research laboratory of a university hospital.
  
  
  METHODS
  Wild-type mice and PAF-receptor knockout mice.
  
  
  METHODS
  Mice received an infusion of normal saline, fish oil- or soybean oil-based lipid emulsions before lipopolysaccharide challenge.
  
  
  RESULTS
  Preinfusion with soybean oil resulted in increased leukocyte invasion, myeloperoxidase activity, and protein leakage and exaggerated release of tumor necrosis factor (TNF)-alpha as well as macrophage inflammatory protein (MIP)-2 into the alveolar space after intratracheal lipopolysaccharide challenge. In contrast, preinfusion with fish oil reduced leukocyte invasion, myeloperoxidase activity, protein leakage, and TNF-alpha as well as MIP-2 generation. Corresponding profiles were found in plasma following intraperitoneal lipopolysaccharide application: Soybean oil increased but fish oil decreased the TNF-alpha and MIP-2 formation. When PAF-receptor-deficient mice were challenged with lipopolysaccharide, leukocyte invasion, lung tissue myeloperoxidase, cytokine generation, and alveolar protein leakage corresponded to those observed in wild-type animals. Fish oil and soybean oil lost their diverging effects on leukocyte transmigration, myeloperoxidase activity, leakage response, and cytokine generation in these knockout mice. Similarly, the differential impact of both lipid emulsions on these lipopolysaccharide-provoked changes was suppressed after pretreating animals with a PAF-receptor antagonist.
  
  
  CONCLUSIONS
  Fish oil- vs. soybean oil-based lipid infusions exert anti- vs. proinflammatory effects in murine models of acute inflammation. The PAF/PAF-receptor-linked signaling appears to be a prerequisite for this differential profile.
authors.affiliation: University of Giessen Lung Center (UGLC), Justus-Liebig-University of Giessen, Giessen, Germany.
authors.forename: Martina Barbara
authors.initials: MB
authors.lastname: Schaefer
authors.forename: Juliane
authors.initials: J
authors.lastname: Ott
authors.forename: Andrea
authors.initials: A
authors.lastname: Mohr
authors.forename: Ming Hua
authors.initials: MH
authors.lastname: Bi
authors.forename: Andrea
authors.initials: A
authors.lastname: Grosz
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mayer
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000628:therapy*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D013024:Soybean Oil / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D013024:Soybean Oil