Prenatal exposure to endotoxin in rats attenuates the allergic airways eosinophil infiltration in the adult offspring: role of inducible nitric oxide synthase activation.
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.
Datti
Fernanda
F
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, PO Box 6111, Campinas 13084-971, SP, Brazil.
Datti
Marcelo
M
Antunes
Edson
E
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004789:Enzyme Activation; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006146:Guanidines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine