title: Group VIB Ca(2+)-independent phospholipase A(2γ) is associated with acute lung injury following trauma and hemorrhagic shock.
abstract: BACKGROUND
  Gut-derived mediators are carried via mesenteric lymph duct into systemic circulation after trauma/hemorrhagic shock (T/HS), thus leading to acute lung injury (ALI)/multiple-organ dysfunction syndrome. Phospholipase A2 (PLA(2)) is a key enzyme for the production of lipid mediators in posthemorrhagic shock mesenteric lymph (PHSML). However, the precise functions of PLA(2) subtype, such as cytosolic PLA(2), secretory PLA(2), and Ca-independent PLA(2), in the acute phase of inflammation have remained unclear. Our previous study has suggested that the activation of Group VIB Ca-independent PLA(2γ) (PLA(2γ)) may be associated with increased lyso-phosphatidylcholines (LPCs) in the PHSML. Therefore, our purpose was to verify the role of iPLA(2γ) on the production of 2-polyunsaturated LPC species and the pathogenesis of T/HS-induced ALI using an iPLA(2γ)-specific inhibitor, R-(E)-6-(bromoethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (R-BEL).
  
  
  METHODS
  Male Sprague-Dawley rats were anesthetized and cannulated in blood vessels and mesenteric lymph duct. Animals in the T/HS group underwent a midline laparotomy plus hemorrhagic shock (mean arterial pressure, 35 mm Hg, 30 minutes) and 2-hour resuscitation with shed blood and 2× normal saline. Trauma/sham shock rats were performed the identical procedure without hemorrhage. R-BEL or DMSO was administered 30 minutes before T/HS or trauma/sham shock. Polyunsaturated LPCs and arachidonic acid in the PHSML were analyzed with a liquid chromatography/electrospray ionization-mass spectrometry. Furthermore, ALI was assessed by lung vascular permeability, myeloperoxidase activity, and histology.
  
  
  RESULTS
  T/HS increased 2-polyunsaturated LPCs and arachidonic acid in the PHSML. The R-BEL pretreatment significantly decreased these lipids and also inhibited ALI.
  
  
  CONCLUSIONS
  The iPLA(2γ) enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.
authors.affiliation: From the Departments of Acute Critical Care and Disaster Medicine (K.M., S.M., Y.O.) and Molecular Pathophysiology (J.K.), Graduate School of Medical and Dental Sciences, and Shock, Trauma and Emergency Medical Center (J.A.), Tokyo Medical and Dental University; and Department of Biology (T.K., Y.Y., K.O.), Faculty of Science, Ochanomizu University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morishita
authors.forename: Junichi
authors.initials: J
authors.lastname: Aiboshi
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Saori
authors.initials: S
authors.lastname: Mikami
authors.forename: Jiro
authors.initials: J
authors.lastname: Kumagai
authors.forename: Keiko
authors.initials: K
authors.lastname: Onisawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Otomo
mesh_terms: D055371:Acute Lung Injury / Q000201:enzymology* / Q000209:etiology / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D014947:Wounds and Injuries / Q000150:complications* / Q000378:metabolism
chemical_list: D054513:Group IV Phospholipases A2