title: Ovalbumin sensitization of guinea pig at birth prevents the ontogenetic decrease in airway smooth muscle responsiveness.
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.
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, 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.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Chitano
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Duke Center for Molecular and Biomolecular Imaging, Duke University Medical Center, Durham, North Carolina Duke Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Simone
authors.initials: S
authors.lastname: Degan
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Worthington
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pozzato
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Syed H
authors.initials: SH
authors.lastname: Hussaini
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Turner
authors.affiliation: James Hogg Research Centre, Institute for Heart and Lung Innovation and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Delbert R
authors.initials: DR
authors.lastname: Dorscheid
authors.affiliation: Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Murphy
keywords: Airway hyperresponsiveness; asthma; maturation; neonatal allergic sensitization; ontogenesis