AIRWAY BIOLOGY OF ASTHMA

哮喘的气道生物学

• 批准号: 2069704
• 负责人: ALAN Richard LEFF
• 金额: $ 66.77万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2069704
• 关键词: asthma; cooperative study; eosinophil; inflammation

The focus of this AAIDCRC application is on the inflammatory pathogenesis of airway hyperresponsiveness that characterizes human asthma. Particular emphasis will be placed upon the pathogenesis of airway hyperreactivity caused by cellular adhesion and activation of eosinophils. The program consists of 3 related projects that focus upon the l) secretory, 2) neurohumoral and 3) hematopoietic aspects of eosinophil function in airway responsiveness. A fourth project is a Demonstration and Education Project (D&E) that is designed to install and assess the efficacy of an education program for an asthma treatment center in the inner city of Chicago. Project 1 aims to assess the role of specific endothelial and matrix protein adhesion reactions on the upregulation of stimulated secretion from immunomagnetically isolated human blood eosinophils. A second aspect of these investigations determines the role of eosinophil secretion that is augmented by ligand/matrix adhesion in inducing in vitro hypercontractility in human airways. Project 2 assesses bidirectional interactions between sensory c-fibers and eosinophils, which amplify cell recruitment and activation. The physiological relevance to airway hyperresponsiveness of these in vitro interactions is evaluated also in two models of guinea pig inflammation m vivo. Project 3 examines in detail the molecular and cellular aspects of eosinopoiesis using a recently developed method for culturing eosinophils in vitro from the umbilical cord blood of neonates. Since eosinopoiesis is the first step in the translocation of these inflammatory cells to the conducting airways, studies are proposed to assess the essential roles of GM- CSF, interleukin (IL)-3 and IL-5 in the in vitro differentiation of bioactive eosinophils. A second series of studies seeks to identify interactions between extracellular matrix factors and eosinophils that influence cytokine-directed eosinopoiesis. Project 4 is a D and E project that tests the hypothesis that self-management instruction through community health workers significantly decreases morbidity and mortality among inner city children with limited health care resources. This program, conducted through the Department of Pediatrics and the La Rabida Children's Hospital, assesses the efficacy of a targeted co-management approach between physician and community health worker in achieving better asthma treatment by altering patient behavior. Data derived from the basic science component of these investigations will provide a coordinated approach to understanding the role of the eosinophil in caring airway hyperresponsiveness. The D & E project utilizes an experienced clinical teacher to apply pharmacological concepts of asthma therapy to a population facing diminishing health care resources. It is anticipated that the studies proposed in these projects will contribute to a mechanistic understanding of the cellular mechanisms that convert normally responsiveness tissues into asthmatic airways and of applying current therapies effectively.

本AAIDCRC应用的重点是炎症 气道高反应性的发病机制， 哮喘将特别强调的发病机制， 细胞粘附和活化引起的气道高反应性 嗜酸性粒细胞该计划包括3个相关项目， 重点关注l）分泌，2）神经体液和3）造血 嗜酸性粒细胞在气道反应性中的作用。第四 示范和教育项目（D&E）， 旨在安装和评估教育计划的有效性， 芝加哥市中心的哮喘治疗中心。 项目1的目的是评估特定的内皮细胞和 基质蛋白粘附反应对刺激的 免疫磁性分离的人血嗜酸性粒细胞分泌物。 这些调查的第二个方面确定了 嗜酸性粒细胞分泌增加的配体/基质粘附， 在人气道中诱导体外过度收缩。计划2 评估感觉c纤维之间的双向相互作用， 嗜酸性粒细胞，其放大细胞募集和激活。的 生理相关的气道高反应性，这些在 还在两种豚鼠模型中评价了体外相互作用 体内炎症。项目3详细研究了分子和 使用最近开发的方法研究细胞内的嗜酸细胞生成 用于体外培养来自脐带血的嗜酸性粒细胞， 新生儿。因为造血是细胞发育的第一步， 这些炎性细胞转移到传导 航空公司，研究建议，以评估转基因的重要作用， CSF、IL-3和IL-5在体外诱导分化为成纤维细胞中的作用 生物活性嗜酸性粒细胞第二系列研究旨在确定 细胞外基质因子与嗜酸性粒细胞的相互作用 影响甜菜碱引导的嗜酸性粒细胞生成。项目4是D 和E项目，测试自我管理的假设， 通过社区卫生工作者的指导， 降低市中心儿童的发病率和死亡率， 有限的医疗资源。该计划通过 儿科和拉比达儿童医院， 评估有针对性的共同管理方法的有效性， 医生和社区卫生工作者在实现更好的哮喘 通过改变患者的行为来治疗。数据来源于基础 这些调查的科学组成部分将提供一个 协调的方法来了解嗜酸性粒细胞在 关心气道高反应性。D & E项目利用了 经验丰富的临床教师应用药理学概念， 哮喘治疗的人口面临减少的医疗保健 资源预计这些研究报告中提出的研究 项目将有助于机械的理解， 将正常反应组织 以及应用当前的治疗方法 有效地

项目成果

Association of granular exocytosis with Ca(2+)-activated K+ channels in human eosinophils.

颗粒胞吐作用与人嗜酸性粒细胞中 Ca(2) 激活的 K 通道的关联。

• DOI: 10.1152/ajplung.1997.273.1.l16
• 发表时间: 1997
• 期刊: The American journal of physiology.
• 作者: Saito,M;Sato,R;Munoz,NM;Herrnreiter,A;Oyaizu,M;Kasugai,H;Narahashi,T;Leff,AR
• 通讯作者: Leff,AR

Differential effects of cyclosporine A after acute antigen challenge in sensitized cats in vivo and ex vivo.

环孢素 A 对致敏猫体内和离体急性抗原攻击后的不同作用。

• DOI: 10.1038/sj.bjp.0701716
• 发表时间: 1998
• 期刊: British journal of pharmacology
• 影响因子: 7.3
• 作者: Mitchell,RW;Cozzi,P;Ndukwu,IM;Spaethe,S;Leff,AR;Padrid,PA
• 通讯作者: Padrid,PA

Assessment of agonist- and cell-mediated responses in airway microsections by computerized videomicrometry.

通过计算机视频显微测量法评估气道显微切片中激动剂和细胞介导的反应。

• DOI: 10.1152/ajplung.1995.268.3.l519
• 发表时间: 1995
• 期刊: The American journal of physiology.
• 作者: Galens,S;Munoz,NM;Rabe,KF;Herrnreiter,A;Mayer,D;Morton,B;McAllister,K;Leff,AR
• 通讯作者: Leff,AR

Airway reopening pressure in isolated rat lungs.

离体大鼠肺部气道重新开放压力。

• DOI: 10.1152/jappl.1994.76.3.1372
• 发表时间: 1994
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Naureckas,ET;Dawson,CA;Gerber,BS;Gaver3rd,DP;Gerber,HL;Linehan,JH;Solway,J;Samsel,RW
• 通讯作者: Samsel,RW

Muscarinic hyperresponsiveness of antigen-sensitized feline airway smooth muscle in vitro.

体外抗原致敏猫气道平滑肌的毒蕈碱高反应性。

• 发表时间: 1997
• 期刊: American journal of veterinary research.
• 作者: Mitchell,RW;Ndukwu,IM;Leff,AR;Padrid,PA
• 通讯作者: Padrid,PA