Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.
AffiliationDepartment of Anesthesia and Intensive Care Medicine, Royal College of Surgeons, of Ireland, Beaumont Hospital Dublin, Ireland.
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CitationJ Surg Res. 2011 Mar 16.
JournalThe Journal of surgical research
AbstractBACKGROUND: 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 A(4) 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 (PGI(2)) analogue. Lung injury was assessed by wet/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) 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 PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.
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