Host Defense Mechanisms in Chronic Lung Disease

慢性肺病的宿主防御机制

• 批准号: 7917413
• 负责人: JO RAE WRIGHT
• 金额: $ 271.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-19 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917413
• 关键词: Host; Defense; Mechanisms; Chronic; Lung

The overall goal of this SCCOR proposal is to elucidate the roles of innate and adaptive immunity in the pathogenesis of chronic lung disease. The SCCOR proposal consists of four interrelated research projects that are focused on two chronic lung diseases: asthma and bronchiolitis obliterans syndrome (BOS) with a common underlying theme of epithelial injury, inflammation, repair and fibroproliferation. The central hypothesis to be tested is that chronic lung disease occurs as a consequence of destructive or maladaptive host responses to common environmental insults that challenge the lung. The fundamental roles of innate and adaptive host responses are to recognize invading antigens, pathogens or altered self components with the purpose of eradicating the offending agents and restoring tissue integrity. While resolution can occur when the host response is normal, an exogenous insult cannot be contained when a critical host factor is inactivated, dysregulated, or becomes dysfunctional. Such maladaptive host responses lead to chronic lung disease. The project specific hypotheses within this SCCOR proposal are: Project 1: Surfactant proteins SP-A and SP-D, which are produced by both alveolar and airway cells, interact with cells of both the adaptive and innate immune systems to coordinately maximize defense against inhaled allergens and that cause and exacerbate asthma, while minimizing an over exuberant immune response that could result in inflammation, tissue damage and chronic lung disease. Project 2: Interleukin 13 (IL-13) modulates airway fibroblast function in human asthma via increased expression of platelet-derived growth factor (PDGF), an adaptive host response, and subsequent airway remodeling via fibroblast proliferation, collagen expression and decreased elastin expression. Project 3: Activation of innate immunity through toll like receptors (TLRs) in the transplanted lung promotes the adaptive alloimmune response leading to acute rejection and BOS. Project 4: Innate immune mechanisms regulate chronic inflammation and tissue remodeling and specifically, host hyaluronan and TLR interactions are critical components of the injury and repair response in non-infectious lung injury, BOS and chronic asthma. These studies will contribute to our understanding of normal and altered host responses on lung structure and function and will provide a basis for investigation and development of new therapies for the treatment of chronic lung diseases.

该SCCOR建议的总体目标是阐明先天和适应性免疫在慢性肺部疾病的发病机理中的作用。 SCCOR提案由四个相互关联的研究项目组成，这些研究项目集中在两种慢性肺部疾病上：哮喘和细支气管炎闭塞综合征（BOS），其上皮损伤，炎症，修复和纤维化促进性的共同基本主题。要检验的中心假设是，由于对挑战肺部挑战的常见环境侮辱的破坏性或适应不良的宿主反应，慢性肺部疾病发生。先天和自适应宿主反应的基本作用是识别入侵的抗原，病原体或改变的自我成分，目的是消除违规药物并恢复组织完整性。虽然当宿主响应正常时可能会发生分辨率，但是当关键宿主因子失活，失调或变功能失调时，不能包含外源性损伤。这种不良适应性宿主的反应导致慢性肺部疾病。 该SCCOR建议中的特定假设是： 项目1：由肺泡和气道细胞产生的表面活性剂蛋白SP-A和SP-D与适应性和先天免疫系统的细胞相互作用，以协调对吸入过敏原的防御，以及导致哮喘的防御，同时使过度炎症的免疫反应最小化，从而导致过度炎症，从而导致炎症和组织损害，并导致组织损害，并在组织中造成损害，并在组织中造成过度损害。 项目2：白介素13（IL-13）通过增加血小板衍生生长因子（PDGF）的表达，自适应宿主反应以及随后的气道通过成纤维细胞增殖，胶原蛋白表达和降低弹性蛋白的表达来调节人类哮喘中的气道成纤维细胞功能。 项目3：移植后的肺中通过类似受体（TLR）激活先天免疫力，促进了适应性的同种免疫反应，导致急性排斥和BOS。 项目4：先天免疫机制调节慢性炎症和组织重塑，具体来说，宿主透明质酸和TLR相互作用是非感染性肺损伤，BOS和慢性哮喘的损伤和修复反应的关键成分。 这些研究将有助于我们理解正常和改变宿主对肺结构和功能的反应，并为研究和开发新疗法的治疗方法提供基础。

项目成果

Toll-like receptors, innate immunity and lung transplantation.

Toll 样受体、先天免疫和肺移植。

• DOI: 10.2741/e58
• 发表时间: 2009
• 期刊: Frontiers in bioscience (Elite edition)
• 作者: Snyder,LaurieD;Palmer,ScottM
• 通讯作者: Palmer,ScottM

Acute allograft rejection: cellular and humoral processes.

• DOI: 10.1016/j.ccm.2011.02.008
• 发表时间: 2011-06
• 期刊: Clinics in chest medicine
• 影响因子: 5.7
• 作者: Martinu T;Pavlisko EN;Chen DF;Palmer SM
• 通讯作者: Palmer SM

Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.

• DOI: 10.1016/j.trim.2014.10.005
• 发表时间: 2015-01
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: Gowdy KM;Martinu T;Nugent JL;Manzo ND;Zhang HL;Kelly FL;Holtzman MJ;Palmer SM
• 通讯作者: Palmer SM

Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation.

• DOI: 10.1111/j.1600-6143.2012.04201.x
• 发表时间: 2012-11
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Kelly FL;Kennedy VE;Jain R;Sindhwani NS;Finlen Copeland CA;Snyder LD;Eu JP;Meltzer EB;Brockway BL;Pavlisko E;Stripp BR;Palmer SM
• 通讯作者: Palmer SM

Allogeneic splenocyte transfer and lipopolysaccharide inhalations induce differential T cell expansion and lung injury: a novel model of pulmonary graft-versus-host disease.

• DOI: 10.1371/journal.pone.0097951
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Martinu T;Kinnier CV;Sun J;Kelly FL;Nelson ME;Garantziotis S;Foster WM;Palmer SM
• 通讯作者: Palmer SM