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Published online before print February 14, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1005596

Received for publication October 21, 2005.
Revised December 9, 2005.
Accepted for publication December 19, 2005.

Article

Tissue-specific expression of estrogen receptors and their role in the regulation of neutrophil infiltration in various organs following trauma-hemorrhage

Huang-Ping Yu ^*, Tomoharu Shimizu ^*, Ya-Ching Hsieh ^*, Takao Suzuki ^*, Mashkoor A. Choudhry ^*, Martin G. Schwacha ^*, and Irshad H. Chaudry ^*@

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

^@ To whom correspondence should be addressed. E-mail: Irshad.Chaudry{at}ccc.uab.edu.

	Abstract

Although 17-estradiol (E2) administration after trauma-hemorrhage (T-H) reduces tissue neutrophil sequestration in male rodents, it remains unknown which of the estrogen receptor (ER) subtypes mediates this effect and whether the same ER subtype is involved in all the tissues. We hypothesized that the salutary effects of E2 on attenuation of neutrophil accumulation following T-H are tissue and receptor subtype-specific. Male Sprague-Dawley rats underwent sham operation or T-H (mean BP, 40 mmHg for 90 min and then resuscitation). E2 (50 µg/kg), ER- agonist propyl pyrazole triol (PPT; 5 µg/kg), ER- agonist diarylpropiolnitrile (DPN; 5 µg/kg), or vehicle (10% dimethyl sulfoxide) was administered subcutaneously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, and intercellular adhesion molecule (ICAM)-1 levels in the liver, intestine, and lung were measured (n=6 rats/group). ER- and ER- mRNA levels in sham-operated rats were also determined. T-H increased MPO activity, CINC-1, CINC-3, and ICAM-1 levels in the liver, intestine, and lung. These parameters were improved significantly in rats receiving E2 after T-H. Administration of the ER- agonist PPT but not the ER- agonist DPN improved the measured parameters in the liver. In contrast, DPN but not PPT significantly improved these parameters in the lung. In the intestine, ER subtype specificity was not observed. ER- mRNA expression was highest in the liver, whereas ER- mRNA expression was greatest in the lung. Thus, the salutary effects of E2 administration on tissue neutrophil sequestration following T-H are receptor subtype and tissue-specific.

Key Words: shock • ICAM-1 • CINC-1 • CINC-3 • propyl pyrazole triol • diarylpropiolnitrile

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