title: Phospholipase A(2)--derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst.
abstract: BACKGROUND
  Our previous work identified posthemorrhagic shock mesenteric lymph (PHSML) lipids as key elements in polymorphonuclear neutrophil (PMN)--provoked acute lung injury. We hypothesize that gut phospholipase A(2) (PLA(2)) is responsible for the generation of proinflammatory lipids in PHSML that primes circulating PMNs for enhanced oxidative burst.
  
  
  METHODS
  Mesenteric lymph was collected from rats (n = 5) before (preshock), during the induction of hemorrhagic shock (mean arterial pressure, 40 mm Hg x 30 minutes), and at resuscitation (shed blood + 2x lactated Ringer's solution). PLA(2) inhibition (quinacrine, 10 mg/kg, intravenously) was given before shock was induced. Extracted lipids were separated by normal phase high-pressure liquid chromatography and resuspended in albumin. PMNs were exposed to a 5% vol:vol concentration of eluted lipids and activated with N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L). Superoxide production was assessed by cytochrome C reduction.
  
  
  RESULTS
  High-pressure liquid chromatography--extracted neutral lipids of lymph collected before hemorrhagic shock did not prime the PMN oxidase, whereas isolated neutral lipids of postshock lymph primed PMNs 2.6- +/- 0.32-fold above baseline (P <.05). PLA(2) inhibition returned PHSML neutral lipid priming to baseline levels.
  
  
  CONCLUSIONS
  PLA(2) inhibition before hemorrhagic shock abrogates the neutrophil priming effects of PHSML through reduction of the accumulation of proinflammatory neutral lipids. Identification of these PLA(2)-dependent lipids provides a mechanistic link that may have therapeutic implications for postshock acute lung injury.
authors.affiliation: Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, Colorado 80204, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Gonzalez
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: D J
authors.initials: DJ
authors.lastname: Ciesla
authors.forename: W L
authors.initials: WL
authors.lastname: Biffl
authors.forename: P J
authors.initials: PJ
authors.lastname: Offner
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism*; D008196:Lymph / Q000201:enzymology* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000276:immunology*; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013897:Thoracic Duct / Q000276:immunology / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013481:Superoxides; D007975:Leukotriene B4; D010741:Phospholipases A; D011796:Quinacrine