RESUMO
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-alpha, and that this cytokine has been implicated in pathogenesis of asthma, we also evaluated whether TNF-alpha plays a role in the allergic airways inflammation by maternal LPS exposure. Pregnant rats were pretreated with the iNOS inhibitor aminoguanidine (50mg/rat per day; given from day 13 of gestation up to delivery) before exposure to LPS (7mug/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 48h 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-alpha 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.
Assuntos
Eosinófilos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Exposição Materna , Óxido Nítrico Sintase Tipo II/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Eosinofilia Pulmonar/imunologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Ativação Enzimática , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Guanidinas/administração & dosagem , Guanidinas/farmacologia , Contagem de Leucócitos , Masculino , Troca Materno-Fetal , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ovalbumina/imunologia , Gravidez , Eosinofilia Pulmonar/patologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The effects of chronic unpredictable stress on airway leukocyte infiltration and plasma extravasation in female rats have been investigated. The chronic stress lasted for 14 days and consisted of transitory and variable changes in the living conditions of the animals. Concomitant to the stress procedure, the animals were sensitized (Day 0) and challenged with ovalbumin (OVA; 200 microg) at Day 14. Bronchoalveolar lavage (BAL) was performed 48 h after intratracheal challenge with OVA (0.4 ml of a 0.25% solution). The increase in plasma extravasation was assessed by the rat paw oedema induced by OVA (0.1 mg/paw) or the mast cell degranulator compound 48/80 (5 microg/paw). A significant increase (P < .05) in the total leukocyte influxes into the airways was observed in the stressed (sensitized) group compared to nonstressed (sensitized) animals, and this was associated with a marked recruitment of eosinophils and mononuclear cells in the BAL fluid. In OVA-sensitized rats, intraplantar injection of OVA induced a marked paw oedema that was significantly higher in stressed compared to nonstressed groups. In contrast to OVA, the compound 48/80 (5 microg/paw)-induced oedema did not significantly differ between nonstressed and stressed groups. Our results indicate that chronic unpredictable stress exacerbates the vascular and cellular inflammatory responses.