ONTOGENY AND SENSITIZATION MEDIATE AIRWAY CONTRACTILITY

哮喘的患病率和表现在儿童时期比 在成年生活中。 研究表明，气道反应性在几个 物种从胎儿期和出生时的最低水平增加到 在几天到几周的时间里， 虽然这样做的原因 差异尚不清楚，先前的调查集中在 少年气道的机械不稳定性和更大的频率， 炎症刺激物如病毒病原体和过敏性 致敏 最近的研究强调了气道通畅的作用， 肌肉（ASM）。 过敏性致敏已被证明大大增加， ASM的缩短速度（VS）和最大缩短。 早期过敏 致敏可能有助于增加反应性在未成熟的 并通过改变正常的呼吸道， ASM收缩表型的成熟变化。 的 应用程序建议调查成熟的机制， 基线和过敏后ASM收缩力的变化 致敏假设：1）幼年ASM增加VS 与婴儿或成人ASM相比， 收缩特性：肌球蛋白轻链激酶（MLCK）增加 浓度在青少年没有同步增加的内部 抗缩短性（IRS）直到成年。2)过敏 卵清蛋白（OA）在青少年中的致敏作用进一步增加 通过增加MLCK水平和阻止正常的收缩力 IRS的增加。3)早期致敏的结果是进一步的 持续到成年的VS增加。 具体目的是：1）确定个体发育对气道的影响 平滑肌缩短;和2）确定过敏性 对缩短的个体发育的敏感性。

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.