Korean J Physiol Pharmacol.  1999 Jun;3(3):263-273.

Effect of the inhibition of phospholipase A2 in generation of free radicals in intestinal ischemia/reperfusion induced acute lung injury

• Lee YM
• Park YY
• Kim T
• Cho HG
• Lee YJ
• Repine JE

Abstract

The role of phospholipase A2 (PLA2) in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific PLA2 inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that PLA2 increases oxidative stresscaused by intestinal I/R. The PLA2 activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of PLA2 suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of PLA2, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

Keyword

Adult respiratory distress syndrome; Intestinal ischemia-reperfusion; PLA 2; Oxidative stress

MeSH Terms

Acute Lung Injury*
Constriction
Free Radicals*
Hydrogen Peroxide
Interleukin-1
Intestines
Ischemia
Leukocytes
Lung
Mesenteric Artery, Superior
Microscopy, Electron
Neutrophils
Oxidative Stress
Peroxidase
Phospholipases A2*
Phospholipases*
Quinacrine
Rats, Sprague-Dawley
Reperfusion
Respiratory Burst
Respiratory Distress Syndrome, Adult
Transferases
Free Radicals
Hydrogen Peroxide
Interleukin-1
Peroxidase
Phospholipases
Phospholipases A2
Quinacrine
Transferases