Perinatal environmental tobacco smoke exposure alters the immune response and airway innervation in infant primates

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:122

Article

Yu, Mang^1,3  Zheng, Xiaomu^1,3  Peake, Janice^1,2,3  Joad, Jesse P.^3,4  Pinkerton, Kent E.^1,2,3,4 

[1] Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA

[2] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA

[3] Univ Calif Davis, Ctr Comparat Resp Biol & Med, Davis, CA 95616 USA

[4] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA

关键词: environmental tobacco smoke;    perinatal exposure;    T(H)2 cytokine;    brain-derived neurotrophic factor;    substance P;    asthma susceptibility;   

DOI  :  10.1016/j.jaci.2008.04.038

来源: Elsevier

【 摘 要 】

Background: Epidemiologic studies associate environmental tobacco smoke (ETS) exposure with childhood asthma. Objective: To investigate whether specific pathophysiological alterations that contribute to asthma development in human beings can be induced in infant monkeys after perinatal ETS exposure. Methods: Rhesus macaque fetuses/infants were exposed to ETS at 1 mg/m(3) of total suspended particulate matter from 50 days gestational age to 2.5 months postnatal age. Inflammatory and neural responses to ETS exposure were measured in the infant monkeys. Results: Perinatal ETS exposure could induce systemic and local responses, which include significant elevation of plasma levels of C5a and brain-derived neurotrophic factor, as well as significant increases in pulmonary expression of proinflammatory cytokine TNF-alpha and T(H)2 cytokine IL-5, chemokine monocyte chemoattractant protein 1, and the density of substance P-positive nerves along the bronchial epithelium. Perinatal ETS exposure also significantly increased the numbers of mast cells, eosinophils, monocytes, and lymphocytes in the lungs of infant monkeys. In addition, ex vivo measurements showed significantly increased levels of IL-4 and brain-derived neurotrophic factor in the culture supernatant of PBMCs. Interestingly, as an important component of cigarette smoke, LPS was detected in the plasma of infant monkeys subjected to perinatal exposure to ETS. In contrast, an inhibitory effect of perinatal ETS exposure was also observed, which is associated with decreased phagocytic activity of alveolar macrophages and a significantly decreased level of nerve growth factor in the bronchoalveolar lavage fluid. Conclusion: Perinatal ETS exposure can induce a T(H)2-biased inflammatory response and alter airway innervation in infant monkeys.

【 授权许可】

Free