Korean J Physiol Pharmacol.  1998 Aug;2(4):479-491.

Effect of the inhibition of platelet activating factor on oxidative lung injury induced by interleukin-1 alpha

Affiliations
  • 1Department of Physiology, School of Medicine, Catholic University of Taegu-Hyosung, Taegu 705-034, South Korea.

Abstract

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin-1alpha (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental
results
showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase A2.

Keyword

Acute lung leak; Interleukin-1; PAF, NFkB; Oxidative stress

MeSH Terms

Acute Lung Injury
Animals
Blood Platelets*
Bronchoalveolar Lavage Fluid
Cytokines
Endothelial Cells
Hydrogen Peroxide
Injections, Intravenous
Insufflation
Interleukin-1*
Interleukin-1alpha*
Lung Injury*
Lung*
Microscopy, Electron
Neutrophils
NF-kappa B
Oxidative Stress
Peroxidase
Phospholipases A2
Platelet Activating Factor*
Rats
Respiratory Burst
Respiratory Distress Syndrome, Adult
Trachea
Cytokines
Hydrogen Peroxide
Interleukin-1
Interleukin-1alpha
NF-kappa B
Peroxidase
Phospholipases A2
Platelet Activating Factor
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