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Group VIB Ca(2+)-independent phospholipase A(2γ) is associated with acute lung injury following trauma and hemorrhagic shock.

AbstractBACKGROUND:
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.
CONCLUSION:
The iPLA(2γ) enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.
AuthorsKoji Morishita, Junichi Aiboshi, Tetsuyuki Kobayashi, Yuri Yokoyama, Saori Mikami, Jiro Kumagai, Keiko Onisawa, Yasuhiro Otomo
JournalThe journal of trauma and acute care surgery (J Trauma Acute Care Surg) Vol. 75 Issue 5 Pg. 767-74 (Nov 2013) ISSN: 2163-0763 [Electronic] United States
PMID24158193 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Group IV Phospholipases A2
Topics
  • Acute Lung Injury (enzymology, etiology, therapy)
  • Animals
  • Disease Models, Animal
  • Group IV Phospholipases A2 (metabolism)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Resuscitation
  • Shock, Hemorrhagic (complications, metabolism, therapy)
  • Wounds and Injuries (complications, metabolism)

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