Chitano Pasquale, Wang Lu, Degan Simone, Worthington Charles L, Pozzato Valeria, Hussaini Syed H, Turner Wesley C, Dorscheid Delbert R, Murphy Thomas M
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.
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.
Physiol Rep. 2014 Dec 11;2(12). doi: 10.14814/phy2.12241. Print 2014 Dec 1.
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.
气道平滑肌(ASM)在幼年时表现出高反应性表型,而在成年后反应性降低。我们推测,引起ASM高反应性且通常发生在生命早期的过敏性致敏会阻止ASM高反应性表型在个体发育过程中的丧失。因此,我们研究了新生儿期过敏性致敏(随后不进行后续过敏原激发)是否会改变ASM特性的个体发育。我们在新生期将豚鼠致敏于卵清蛋白,并在1周、3周和3个月(成年)时对其进行研究。离体气管环的舒尔茨 - 戴尔反应证实了致敏。评估了血液和大气道黏膜下层的炎症发生情况。我们将气管条中ASM的功能评估为产生力和缩短的能力。还研究了波形蛋白在ASM中的含量。在所有3周及以上的致敏动物中均观察到舒尔茨 - 戴尔反应。轻度炎症过程的特征是血液和气道黏膜下层出现嗜酸性粒细胞增多。生命早期致敏对ASM产生力没有影响,但阻止了缩短速度在个体发育过程中的下降以及对缩短阻力的增加。波形蛋白在对照动物中随年龄增加,而在致敏动物中则不然。出生时的过敏性致敏且无后续过敏原暴露足以阻止ASM的正常个体发育,导致ASM高反应性表型持续至成年。