期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 79, 期 5, 页码 963-970出版社
WILEY
DOI: 10.1189/jlb.1005596
关键词
shock; ICAM-1; CINC-1; CINC-3; propyl pyrazole triol-diarylpropiolnitrile
资金
- NIAID NIH HHS [K02 AI49960] Funding Source: Medline
- NIGMS NIH HHS [R37 GM39519] Funding Source: Medline
Although 17 beta-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 blood pressure, 40 mmHg for 90 min and then resuscitation). E2 (50 mu g/kg), ER-alpha agonist propyl pyrazole triol (PPT; 5 mu g/kg), ER-beta agoinist diarylpropiolnitrile (DPN; 5 mu g/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-alpha and ER-beta mRNA levels in sham-operated rats were also determined. T-H increased MPO activity, CINC-1, CINC-1, 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-alpha agonist PPT but not the ER-beta 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-beta mRNA expression was highest in the liver, whereas ER-beta 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.
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