• Lawrence N Diebel and David M Liberati.
• Department of Surgery, Wayne State University, Detroit, Michigan, USA. ldiebel@med.wayne.edu
• J Trauma. 2011 Sep 1;71(3):656-62; discussion 662.

BackgroundFemale gender may protect against infectious complications after injury. This protection may be due to a beneficial effect of estrogen (E2) as the salutary effects are age and estrus cycle related. However, outcome may be worse in females developing infectious complications or organ failure after injury. To assess the role of E2 in postshock organ failure, we studied the effect of E2 on parameters of lung injury in an in vitro cell culture model.MethodsConfluent HT-29 intestinal epithelial cells were established in a two chamber culture system. E2 (1.0 μmol/L) was added in subsets for 72 hours. A commensal strain of Escherichia coli was then added to the apical chamber and cell cultures subjected to normoxic (21% O₂) or hypoxic (5%O₂ × 90 minutes) reoxygenation (H/R) for 3 hours. HT-29 cell culture supernatants were then cocultured with human pulmonary microvascular endothelial cell (HMVEC) monolayers for 90 minutes. HMVEC injury was indexed by apoptosis determined by flow cytometry, permeability to fluorescein isothiocyanate (FITC)-albumin, and intercellular adhesion molecule (ICAM)-1 expression determined by flow cytometry. HMVEC monolayer integrity was indexed by transepithelial electrical resistance.ResultsApoptosis was increased within HMVEC treatment groups at the highest E2 concentrations. HMVEC permeability to albumin was increased after exposure to either E2 or dihydrotestosterone only at the 1.0 μmol/L concentration. However, the magnitude of HMVEC permeability was greatest with E2 at the higher concentration. A similar effect was noted in cells exposed to H/R. ICAM expression was increased by E2 at both concentrations. The most profound increase in ICAM expression occurred in HT-29 cells treated with E2 and H/R exposure. These effects were partially abrogated by the addition of secretory IgA.ConclusionExposure of HT-29 cells to either H/R or E2 had a deleterious effect on HMVEC monolayers. In addition, there seemed to be a synergistic effect of H/R and E2 on pulmonary endothelial injury. This study supports the findings noted in recent clinical studies suggesting E2 decreases infectious complications but may be associated with poorer outcomes if complications occur.

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