Objective: One third of asthmatic women report a decreased expiratory peak flow during menses. Since asthma is characterized by lung inflammation and bronchopulmonary hyperresponsiveness, we investigated the role played by estradiol in allergic lung inflammation. Methods: Cell migration to the lungs of allergic female rats subjected to oophorectomy (OVx) was compared to that in their sham-operated (sham) control counterparts. Seven days after OVx or sham operation, the rats were sensitized intraperitoneally with ovalbumin (OA, 1 mg/kg) suspended in aluminum hydroxide (day 0). At day 7, a subcutaneous booster of OA was performed and an aerosolized OA challenge was carried out at day 14. One day later (day 15), the rats were killed and cell counts were performed in bronchoalveolar lavages (BAL), in peripheral blood and in bone marrow lavages. Results: After the antigen challenge, OVx rats showed a significant decrease in cell migration to the lung as compared to sham-operated rats. Differential analyses of BAL revealed a reduced number of eosinophils, mononuclear cells and neutrophils. In contrast, in bone marrow as well as in the peripheral blood the numbers of eosinophils, mononuclear cells and neutrophils were increased relative to sham controls. Mast cell numbers were similar in both groups. The estradiol receptor antagonist tamoxifen decreased the allergic lung inflammation in intact rats down to levels similar to those found in untreated OVx rats. In contrast, 17β-estradiol replacement in OVx rats reestablished the allergic lung inflammation, as observed by an elevated number of eosinophils, mononuclear cells and neutrophils recovered in BAL. Similarly, an elevated number of inflammatory cells were quantified in BAL from allergic OVx rats when corticosterone effects were blocked with metyrapone or RU-486. Conclusion: Our results suggest that estradiol has proinflammatory actions on the allergic lung response, and these actions seem to be mediated, at least in part, by endogenous glucocorticoids.

No abstract

No abstract

BACKGROUND: Rat trachea display a differential topographical distribution of connective tissue mast cells (CTMC) and mucosal mast cells (MMC) that may imply regional differences in the release of allergic mediators such as tumor necrosis factor-alpha (TNF-alpha) and eicosanoids. AIM: To evaluate the role of CTMC and MMC for release of TNF-alpha and eicosanoids after allergenic challenge in distinct segments of rat trachea. MATERIALS AND METHODS: Proximal trachea (PT) and distal trachea (DT) from ovalbumin (OVA)-sensitized rats, treated or not with compound 48/80 (48/80) or dexamethasone, were incubated in culture medium. After OVA challenge, aliquots were collected to study release of TNF-alpha and eicosanoids. RESULTS: Release of TNF-alpha by PT upon OVA challenge peaked at 90 min and decayed at 6 and 24 h. Release from DT peaked at 30-90 min and decayed 6 and 24 h later. When CTMC were depleted with 48/80, OVA challenge exacerbated the TNF-alpha release by PT at all time intervals, while DT exacerbated TNF-alpha levels 6 and 24 h later only. Dexamethasone reduced TNF-alpha production after 90 min of OVA challenge in PT and at 3 and 6h in DT. OVA challenge increased prostaglandin D2) in DT and leukotriene B4 in both segments but did not modify prostaglandin E2 and leukotriene C4 release. CONCLUSION: OVA challenge induces TNF-alpha release from MMC, which is negatively regulated by CTMC. The profile of TNF-alpha and eicosanoids depends on the time after OVA challenge and of the tracheal segment considered.