Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma

LIFE SCIENCES

卷:89

Article

Kirsten, Thiago Berti¹  Soares de Oliveira, Beatriz Petri²  Ligeiro de Oliveira, Ana Paula³  Kieling, Karin¹  de Lima, Wothan Tavares⁴  Palermo-Neto, Joao¹  Bernardi, Maria Martha^1,2 

[1] Univ Sao Paulo, Dept Pathol, Sch Vet Med, Neuroimmunomodulat Res Grp, BR-05508000 Sao Paulo, Brazil

[2] Univ Paulista, Hlth Sci Inst, Fac Vet Med, Sao Paulo, Brazil

[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo, Brazil

[4] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo, Brazil

关键词: Endotoxin;    Hygiene hypothesis;    Lung allergic inflammation;    OVA;    Rat;   

DOI  :  10.1016/j.lfs.2011.04.023

来源: Elsevier

【 摘 要 】

Aims: There has been emerging interest in the prenatal determinants of respiratory disease. In utero factors have been reported to play a role in airway development, inflammation, and remodeling. Specifically, prenatal exposure to endotoxins might regulate tolerance to allergens later in life. The present study investigated whether prenatal lipopolysaccharide (LPS) administration alters subsequent offspring allergen-induced inflammatory response in adult rats. Main methods: Pregnant Wistar rats were treated with LPS (100 mu g/kg, i.p.) on gestation day 9.5 and their ovariectomized female offspring were sensitized and challenged with OVA later in adulthood. The bronchoalveolar lavage (BAL) fluid, peripheral blood, bone marrow leukocytes and passive cutaneous anaphylaxis were evaluated in these 75-day-old pups. Key findings: OVA sensitized pups of NaCl treated rats showed an increase of leucocytes in BAL after OVA challenge. This increase was attenuated, when mothers were exposed to a single LPS injection early in pregnancy. Thus, LPS prenatal treatment resulted in (1) lower increased total and differential (macrophages, neutrophils, eosinophils and lymphocytes) BAL cellularity count; (2) increased number of total, mononuclear and polymorphonuclear cells in the peripheral blood; and (3) no differences in bone marrow cellularity or passive cutaneous anaphylaxis. Significance: In conclusion, female pups treated prenatally with LPS presented an attenuated response to experimentally-induced asthma. We observed reduced immune cell migration from peripheral blood to the lungs, with no effect on the production of bone marrow cells or antibodies. It was suggested that inflammatory events such as exposure to LPS in early fetal life can attenuate allergic inflammation in the lung, which is a common symptom in asthma. (C) 2011 Elsevier Inc. All rights reserved.

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