ONTOGENY AND SENSITIZATION MEDIATE AIRWAY CONTRACTILITY

儿童时期哮喘的患病率和表现比 在成人生活中。研究表明，几种情况下的呼吸道反应性 物种从胎儿生命和出生期间的最低水平增加到 在几天到几周内达到相当高的水平。虽然这样做的原因 不同之处尚不清楚，此前的调查重点是 青少年呼吸道的机械不稳定性和较高的频率和 病毒病原体和过敏等炎性刺激的影响 敏化。最近的研究强调了呼吸道通畅的作用 肌肉(ASM)。过敏性疾病的致敏性大大增加 ASM的缩短速度(VS)和最大缩短。早期过敏 敏感化可能是未成熟脑中反应性增强的原因之一。 航空公司和通过改变正常状态授予永久性高反应性 ASM收缩表型的成熟变化。这个 应用建议研究成熟化的机制 基础状态和过敏后ASM收缩性能的变化 敏化。这些假设是：1)青少年的ASM比 与婴儿或成人ASM相比，由于对立的差异 收缩特性：肌球蛋白轻链激酶(MLCK)增加 体内浓度没有同步增加的幼鱼 成年前抵抗缩短(IRS)。2)过敏 卵清蛋白(OA)对青少年的致敏作用进一步增强 通过增加MLCK水平和防止正常的 增加美国国税局。3)早期敏化的结果是进一步的 VS的增加会持续到成年生活。 具体目标是：1)确定个体发育对呼吸道的影响 2)测定变态反应的效果。 对缩短性个体发育的敏化。

The prevalence and expression of asthma is greater during childhood than in adult life. Studies indicate that airway reactivity in several species increases from minimal levels during fetal life and birth to a substantial level in a few days to weeks. While reasons for this difference are unclear, prior investigations have focused on the mechanical instability of juvenile airways and the greater frequency and impact of inflammatory stimuli such as viral pathogens and allergic sensitization. More recent studies emphasized the role of airway smooth muscle (ASM). Allergic sensitization has been shown greatly to increase shortening velocity (VS) and maximal shortening in ASM. Early allergic sensitization may contribute to the increased reactivity in immature airways and confer permanent hyperresponsiveness by altering normal maturational changes in the contractile phenotype of ASM. The application proposes to investigate the mechanism of maturational changes in ASM contractility at baseline and after allergic sensitization. The hypotheses are: 1) Juvenile ASM has increased VS compared to infant or adult ASM due to differences in opposing contractile properties: increases in myosin light chain kinase (MLCK) concentration in juveniles without a synchronous increase in internal resistance of shortening (IRS) until adult life. 2) Allergic sensitization with ovalbumin (OA) in juveniles further increases contractility by increasing levels of MLCK and preventing the normal increase in IRS. 3) The consequence of early sensitization is a further increase in VS that persists into adult life. The specific aims are: 1) Determine the effect of ontogeny on airway smooth muscle shortening; and 2) Determine the effect of allergic sensitization on the ontogeny of shortening.