title: Cyclooxygenase-2 suppresses polymorphonuclear neutrophil apoptosis after acute lung injury.
abstract: BACKGROUND
  Polymorphonuclear neutrophil (PMN) apoptosis is suppressed after acute lung injury (ALI), and strategies aimed at inducing PMN apoptosis are thought to be promising therapies for ALI. However, the mechanisms underlying PMN apoptotic suppression are unknown. Cyclo-oxygenase-2 (COX-2) has been shown to regulate tumor cell apoptosis and is up-regulated by inflammatory mediators in PMN. Therefore, we set out to determine whether up-regulation of COX-2 expression contributes to PMN apoptosis after ALI.
  
  
  METHODS
  Experimental ALI was established in New Zealand rabbits by blunt chest trauma, and a correlation analysis of COX-2 immunohistochemical staining in lung tissue and PMN apoptosis in bronchoalveolar lavage fluid (BALF) was performed. Apoptosis was measured by flow cytometric analysis of annexin V and propidium iodide dual staining. As an in vitro correlate, normal PMNs were treated with BALF from injured lung (BALFALI) in the presence or absence of the COX-2 inhibitor, NS398. COX-2 mRNA levels and PMN apoptosis were then measured.
  
  
  RESULTS
  PMN apoptosis was significantly decreased in BALF after injury. In contrast, COX-2 expression was significantly increased after injury. COX-2 protein expression and PMN apoptosis exhibited a strong inverse correlation (gamma = -0.75, p < 0.01). In vitro experiments revealed apoptosis of normal PMNs was significantly decreased by the addition of BALFALI. The addition of BALFALI was also associated with increased COX-2 mRNA levels. Treatment of cultures with NS398, 10 minutes before BALFALI addition, partially reversed all of these effects.
  
  
  CONCLUSIONS
  Up-regulation of intrapulmonary COX-2 expression contributes to the suppression of PMN apoptosis after ALI.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jinzhou
authors.forename: He
authors.initials: H
authors.lastname: Tao
authors.forename: Chen
authors.initials: C
authors.lastname: Wensheng
authors.forename: Wang
authors.initials: W
authors.lastname: Wen
authors.forename: Liu
authors.initials: L
authors.lastname: Jincheng
authors.forename: Cui
authors.initials: C
authors.lastname: Qin
authors.forename: Zhu
authors.initials: Z
authors.lastname: Hailong
authors.forename: Liu
authors.initials: L
authors.lastname: Weiyong
authors.forename: Yi
authors.initials: Y
authors.lastname: Dinghua
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D052246:Cyclooxygenase 2 Inhibitors