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Am J Physiol Lung Cell Mol Physiol 291: L400-L406, 2006. First published March 23, 2006; doi:10.1152/ajplung.00537.2005
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Maintenance of lung myeloperoxidase activity in proestrus females after trauma-hemorrhage: upregulation of heme oxygenase-1

Huang-Ping Yu,1,2 Shaolong Yang,1 Ya-Ching Hsieh,1 Mashkoor A. Choudhry,1 Kirby I. Bland,1 and Irshad H. Chaudry1

1Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

Submitted 22 December 2005 ; accepted in final form 15 March 2006

Previous studies showed that females in the proestrus stage of the reproductive cycle maintain organ functions after trauma-hemorrhage. However, it remains unknown whether the female reproductive cycle is an important variable in the regulation of lung injury after trauma-hemorrhage and, if so, whether the effect is mediated via upregulation of heme oxygenase (HO)-1. To examine this, female Sprague-Dawley rats during diestrus, proestrus, estrus, and metestrus phases of the reproductive cycle or 14 days after ovariectomy underwent soft tissue trauma and then hemorrhage (mean blood pressure 40 mmHg for 90 min followed by fluid resuscitation). At 2 h after trauma-hemorrhage or sham operation, lung myeloperoxidase (MPO) activity and intercellular adhesion molecule (ICAM)-1, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and HO-1 protein levels were measured. Plasma 17beta-estradiol concentration was also determined. The results indicated that trauma-hemorrhage increased lung MPO activity and ICAM-1, CINC-1, and CINC-3 levels in ovariectomized females. These parameters were found to be similar to sham-operated animals in proestrus female rats subjected to trauma-hemorrhage. Lung HO-1 protein level in proestrus females was increased significantly compared with female rats subjected to trauma-hemorrhage during diestrus, estrus, and metestrus phases of the reproductive cycle and ovariectomized rats. Furthermore, plasma 17beta-estradiol level was highest in proestrus females. Administration of the HO inhibitor chromium mesoporphyrin prevented the attenuation of shock-induced lung damage in proestrus females. Thus these findings suggest that the female reproductive cycle is an important variable in the regulation of lung injury following trauma-hemorrhage and that the protective effect in proestrus females is likely mediated via upregulation of HO-1.

hemorrhagic shock; cytokine-induced neutrophil chemoattractant-1; cytokine-induced neutrophil chemoattractant-3; intercellular adhesion molecule-1



Address for reprint requests and other correspondence: I. H. Chaudry, Ctr. for Surgical Research, Univ. of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Rm. G094, Birmingham, AL 35294-0019 (e-mail: irshad.chaudry{at}ccc.uab.edu)




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