Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A₄-Mediated Effect

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• 作者：Michael Scully ; M.B.^&lowast ; ; Chen Gang ; Ph.D.^&dagger ; ; Claire Condron ; Ph.D.^&dagger ; ; David Bouchier-Hayes ; M.Ch.^&dagger ; ; Anthony J. Cunningham ; M.D.^&lowast ; ; ^{anthonyc@rcsi.ie}
• 关键词：cyclooxygenase ; lipoxin ; lung ; ischemic/reperfusion ; iloprost
• 刊名：Journal of Surgical Research
• 出版年：2012
• 出版时间：1 June, 2012
• 年：2012
• 卷：175
• 期：1
• 页码：176-184
• 全文大小：505 K

文摘

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Background

Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia/reperfusion (I/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A₄ in experimental I/R-mediated lung injury.

Materials and Methods

Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I/R group); (3) I/R and SC236, a selective COX-2 inhibitor; (4) I/R and aspirin; and (5) I/R and iloprost, a prostacyclin (PGI₂) analogue. Lung injury was assessed by wet/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE₂, 6-keto-PGF₁¦Á (a hydrolysis product of prostacyclin), lipoxin A₄, and 15-epi-lipoxin A₄ were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed.

Results

I/R significantly increased tissue MPO, the wet/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I/R increased COX-2 immunostaining and both PGE₂ and 6-keto-PGF_1¦Á levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A₄ compared with I/R alone. Iloprost markedly increased lipoxin A₄ levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A₄ levels.

Conclusions

Lipoxin A₄ warrants further evaluation as a mediator of COX-2 regulated lung protection.