HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
批准号:
6391238
负责人:
Sanjay Sethi
金额:
$22.04万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-09-29 至 2004-08-31
关键词:
Haemophilus influenzae alveolar macrophages antigen antibody reaction bacteria infection mechanism bacterial antigens bacterial proteins biopsy bronchoscopy chronic obstructive pulmonary disease clinical research computed axial tomography cytokine diagnostic respiratory lavage elastases enzyme linked immunosorbent assay human subject immunocytochemistry inflammation membrane proteins organ culture pathologic process polymerase chain reaction respiratory infections smoking thoracic radiography tobacco abuse
中文摘要
描述(改编自申请人的摘要)
呼吸道炎症在COPD发病机制中的作用
得到了越来越多的认可。非分型流感嗜血杆菌(NTHI)
COPD患者肺部最常见的细菌病原体是
在这种疾病的所有阶段都存在。NTHI及其组件有许多
对呼吸道组织的促炎作用。尽管如此,NTHI的作用
作为COPD炎症的一种独立刺激因素还没有被探索。
肺泡巨噬细胞是宿主与NTHI相互作用的关键细胞。
此外,肺泡巨噬细胞对炎症刺激有明显的反应。
与肺外组织的巨噬细胞不同。然而,肺泡的相互作用
携带NTHI的巨噬细胞及其对COPD发病机制的影响
未知。研究人员建议进行旨在获得更广泛洞察力的研究
探讨NTHI介导COPD炎症的免疫学机制。
对于所有研究,将招募三组受试者:a)前者
患有慢性阻塞性肺病的吸烟者;b)没有慢性阻塞性肺病的既往吸烟者;以及c)健康的非吸烟者。
在具体目标1中,NTHI“殖民化”与
气道腔和组织中的炎性细胞和介质将
下定决心。炎性细胞因子和弹性蛋白酶将在
将对支气管肺泡灌洗液(BAL)液和炎症细胞进行计数
在BAL和支气管粘膜下层。支气管肺泡灌洗液和支气管活检组织中的NTHI
将通过培养、聚合酶链式反应和免疫染色进行检测。在具体目标2中,
NTHI外膜抗原对肺泡的生物学作用
巨噬细胞功能将被测定。诱导调节性细胞因子,
肺泡巨噬细胞黏附分子和功能的研究
将评估具有免疫活性的NTHI抗原。炎症性和
功能参数将与同一宿主血液的反应进行比较-
衍生的单核巨噬细胞。整合型细菌和细菌的鉴定
促进COPD免疫介导性炎症的宿主成分将
最终导致改变疾病进展的新治疗策略
并改善慢性阻塞性肺疾病的预后。
英文摘要
DESCRIPTION (adapted from the applicants' abstract)
The contribution of airway inflammation to the pathogenesis of COPD has
received increasing recognition. Nontypeable Haemophilus influenzae (NTHI) is
the most common bacterial pathogen in the lungs of patients with COPD, and is
present in all stages of this disease. NTHI and its components have numerous
proinflammatory effects on respiratory tissues. Nonetheless, the role of NTHI
as an independent stimulus to inflammation in COPD has not been explored.
Alveolar macrophages are critical to host interactions with NTHI.
Furthermore, alveolar macrophages respond to inflammatory stimuli distinctly
unlike macrophages of extra-pulmonary tissues. Yet interactions of alveolar
macrophages with NTHI, and the impact on pathogenesis of COPD, remains
unknown. The investigators propose studies designed to gain broader insight
into the immunologic mechanisms by which NTHI mediates inflammation in COPD.
For all studies, three groups of subjects will be recruited: a) former
smokers with COPD; b) former smokers without COPD; and c) healthy non-smokers.
In Specific Aim 1, the association between NTHI 'colonization' and levels of
inflammatory cells and mediators, in the airway lumen and in tissues, will be
determined. Inflammatory cytokines and elastase will be measured in
bronchoalveolar lavage (BAL) fluid and inflammatory cells will be enumerated
in BAL and in bronchial submucosa. NTHI in the BAL and bronchial biopsies
will be detected by culture, PCR and by immunostaining. In Specific Aim 2,
the biological effects of outer membrane antigens of NTHI on alveolar
macrophage function will be determined. Induction of regulatory cytokines,
adhesion molecules and functional capabilities of alveolar macrophages by
immunologically active NTHI antigens will be evaluated. Inflammatory and
functional parameters will be compared with responses of same-host blood-
derived mononuclear phagocytes. Identification of the integral bacterial and
host components that contribute to immune-mediated inflammation in COPD will
ultimately lead to novel therapeutic strategies to alter disease progression
and improve outcome in COPD.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Bacterial Infection in COPD
-
批准号:8045147
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Bacterial Infection in COPD
-
批准号:8391088
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Bacterial Infection in COPD
-
批准号:8586872
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Bacterial Infection in COPD
-
批准号:8196313
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
-
批准号:7008641
-
项目类别:
-
资助金额:$31.43万
-
财政年份:2005
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
-
批准号:7471399
-
项目类别:
-
资助金额:$39.29万
-
财政年份:2005
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
-
批准号:7119519
-
项目类别:
-
资助金额:$39.83万
-
财政年份:2005
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
-
批准号:7663184
-
项目类别:
-
资助金额:$30.68万
-
财政年份:2005
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
-
批准号:7266876
-
项目类别:
-
资助金额:$39.38万
-
财政年份:2005
-
负责人:Sanjay Sethi
-
依托单位:
HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
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批准号:6285816
-
项目类别:
-
资助金额:$22.04万
-
财政年份:2000
-
负责人:Sanjay Sethi
-
依托单位:
HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
-
批准号:6619878
-
项目类别:
-
资助金额:$22.04万
-
财政年份:2000
-
负责人:Sanjay Sethi
-
依托单位:
HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
-
批准号:6527732
-
项目类别:
-
资助金额:$22.04万
-
财政年份:2000
-
负责人:Sanjay Sethi
-
依托单位:
海外基金