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 A2 (PLA2) 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 × 30 minutes), and at resuscitation (shed blood + 2× lactated Ringer's solution). PLA2 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 μmol/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). PLA2 inhibition returned PHSML neutral lipid priming to baseline levels. Conclusions. PLA2 inhibition before hemorrhagic shock abrogates the neutrophil priming effects of PHSML through reduction of the accumulation of proinflammatory neutral lipids. Identification of these PLA2-dependent lipids provides a mechanistic link that may have therapeutic implications for postshock acute lung injury. (Surgery 2001;130:198-203.)
Published Version
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