Group IIA phospholipase A2 mediates lung injury in intestinal ischemia-reperfusion.

Abstract

OBJECTIVE:

To assess the mechanistic role of group IIA phospholipase A2 (PLA2) in the process of local and distant organ injury after intestinal ischemia-reperfusion.

SUMMARY BACKGROUND DATA:

Intestinal ischemia-reperfusion produces lung injury by a mechanism that involves PLA2 activation, but it is unclear which isozyme is responsible for this phenomenon. Group IIA PLA2, one of the secreted forms of PLA2, is known to play a pivotal role in a variety of inflammatory reactions.

METHODS:

Rats underwent 45 minutes of superior mesenteric artery occlusion in the presence and absence of pretreatment with group IIA PLA2 inhibitor, S-5920/LY315920Na (20 mg/kg, subcutaneously, 30 minutes before clamping). At 2 hours of reperfusion, intestinal and lung leak was assessed by 125I-albumin tissue/blood ratio, and liver injury was estimated by serum alanine aminotransferase. PLA2 activities in tissues and sera were quantitated by phosphatidyl-glycerol/sodium cholate mixed micelle assay. PLA2 activities in tissues were also measured after in vitro preincubation with EDTA, S-5920/LY315920Na, or antirat group IIA PLA2 antibody.

RESULTS:

Intestinal ischemia-reperfusion provoked intestinal leak, liver injury, and lung leak, whereas tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities were increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera and only abolished lung leak. The in vitro experiment revealed that most of the intestinal and lung PLA2 activities were inhibited by EDTA, S-5920/LY315920Na, and antirat group IIA PLA2 antibody, but hepatic PLA2 activity was not.

CONCLUSION:

Intestinal ischemia-reperfusion appears to produce lung injury by a mechanism that involves group IIA PLA2 activation. Intestinal ischemia-reperfusion is likely to promote intestinal and hepatic injury independent of group IIA PLA2.

• Authors: K Koike, Y Yamamoto, Y Hori, T Ono
• Journal: Annals of surgery (Ann Surg) Vol. 232 Issue 1 Pg. 90-7 (Jul 2000) ISSN: 0003-4932 [Print] United States
• PMID: 10862200 (Publication Type: Journal Article)

Chemical References

• Acetates
• Indoles
• Keto Acids
• varespladib
• Phospholipases A
• Phospholipases A2

Topics

• Acetates (pharmacology)
• Animals
• Disease Models, Animal
• Humans
• Indoles (pharmacology)
• Intestines (blood supply, enzymology)
• Keto Acids
• Liver (enzymology)
• Lung (enzymology)
• Male
• Phospholipases A (antagonists & inhibitors, physiology)
• Phospholipases A2
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (physiopathology)
• Respiratory Distress Syndrome (physiopathology)