Prenatal exposure to endotoxin in rats attenuates the allergic airways eosinophil infiltration in the adult offspring: Role of inducible nitric oxide synthase activation
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- 作者：Fern ; a Datti ; Marcelo Datti ; Edson Antunes
- 关键词：Prenatal exposure ; Allergy ; Aminoguanidine ; Bone marrow ; Pregnancy
- 刊名：Pulmonary Pharmacology & Therapeutics
- 出版年：2008
- 出版时间：April 2008
- 年：2008
- 卷：21
- 期：2
- 页码：349-355
- 全文大小：310 K
文摘
A correlation between stressful events experienced by the mother during pregnancy and progression of respiratory disease in descendants has been reported. Prenatal exposure to lipopolyssacharide (LPS) reduces allergic airway inflammation in mice offspring. In this study we investigated whether reduction of airways inflammation by maternal LPS exposure involves activation of inducible nitric oxide synthase (iNOS) at prenatal life. Since LPS also induces the release of TNF-α, and that this cytokine has been implicated in pathogenesis of asthma, we also evaluated whether TNF-α plays a role in the allergic airways inflammation by maternal LPS exposure. Pregnant rats were pretreated with the iNOS inhibitor aminoguanidine (50 mg/rat per day; given from day 13 of gestation up to delivery) before exposure to LPS (7 μg/kg, given at day 17 of gestation). At adult ages, female and male offspring were sensitized with ovalbumin (OVA), and 14 days later they were challenged with this allergen. OVA challenge in sensitized offspring increased markedly the eosinophil number in bronchoalveolar lavage (BAL) fluid at 48 h compared with the non-sensitized group. However, the eosinophil number was largely reduced in offspring from maternal LPS exposure, irrespective of offspring gender. Maternal pretreatment with aminoguanidine fully reversed the eosinophil suppression by LPS. The maternal LPS exposure also reduced the eosinophil number in bone marrow and peripheral blood of offspring, but this was not affected by aminoguanidine. No differences in TNF-α levels in BAL fluid were found. In conclusion, our study shows that maternal LPS exposure markedly reduces allergic airways eosinophil recruitment in adult offspring by mechanisms possibly involving iNOS activation.