Ovalbumin sensitization of guinea pig at birth prevents the ontogenetic decrease in airway smooth muscle responsiveness

Physiological Reports

Pasquale Chitano³  Lu Wang³  Simone Degan¹  Charles L. Worthington³  Valeria Pozzato³  Syed H. Hussaini³  Wesley C. Turner³  Delbert R. Dorscheid² 

[1] Duke Center for Molecular and Biomolecular Imaging, Duke University Medical Center, Durham, North Carolina;James Hogg Research Centre, Institute for Heart and Lung Innovation and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina

关键词: Airway hyperresponsiveness;    asthma;    maturation;    neonatal allergic sensitization;    ontogenesis;   

DOI  :  10.14814/phy2.12241

来源: Wiley

【 摘 要 】

Abstract

Airway smooth muscle (ASM) displays a hyperresponsive phenotype at young age and becomes less responsive in adulthood. We hypothesized that allergic sensitization, which causes ASM hyperresponsiveness and typically occurs early in life, prevents the ontogenetic loss of the ASM hyperresponsive phenotype. We therefore studied whether neonatal allergic sensitization, not followed by later allergen challenges, alters the ontogenesis of ASM properties. We neonatally sensitized guinea pigs to ovalbumin and studied them at 1 week, 3 weeks, and 3 months (adult). A Schultz-Dale response in isolated tracheal rings confirmed sensitization. The occurrence of inflammation was evaluated in the blood and in the submucosa of large airways. We assessed ASM function in tracheal strips as ability to produce force and shortening. ASM content of vimentin was also studied. A Schultz-Dale response was observed in all 3-week or older sensitized animals. A mild inflammatory process was characterized by eosinophilia in the blood and in the airway submucosa. Early life sensitization had no effect on ASM force generation, but prevented the ontogenetic decline of shortening velocity and the increase in resistance to shortening. Vimentin increased with age in control but not in sensitized animals. Allergic sensitization at birth without subsequent allergen exposures is sufficient to prevent normal ASM ontogenesis, inducing persistence to adulthood of an ASM hyperresponsive phenotype.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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