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)
气道炎症在COPD发病机制中的作用,
得到越来越多的认可。 无法分型的流感嗜血杆菌(NTHI)是
COPD患者肺部最常见的细菌病原体,
存在于这种疾病的各个阶段。 NTHI及其组件具有许多
对呼吸组织的促炎作用。 然而,NTHI的作用
作为COPD炎症的独立刺激因素尚未进行研究。
肺泡巨噬细胞对宿主与NTHI的相互作用至关重要。
此外,肺泡巨噬细胞对炎症刺激的反应明显
与肺外组织的巨噬细胞不同。 然而,
巨噬细胞与NTHI的关系,以及对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见解的研究
NTHI介导COPD炎症的免疫机制。
对于所有研究,将招募三组受试者:
患有COPD的吸烟者; B)没有COPD的前吸烟者;和c)健康的非吸烟者。
在具体目标1中,NTHI“定殖”与
气道腔和组织中的炎性细胞和介质,
测定 炎症细胞因子和弹性蛋白酶将在
计数支气管肺泡灌洗液(BAL)和炎性细胞
在BAL和支气管粘膜下层。 BAL和支气管活检中的NTHI
将通过培养、PCR和免疫染色进行检测。 在具体目标2中,
NTHI外膜抗原的生物学效应
将测定巨噬细胞功能。 诱导调节性细胞因子,
粘附分子和肺泡巨噬细胞的功能能力
将评价免疫活性NTHI抗原。 炎性和
将功能参数与相同宿主血液的反应进行比较,
衍生的单核吞噬细胞。 鉴定完整的细菌和
导致COPD中免疫介导炎症的宿主成分将
最终导致改变疾病进展的新治疗策略
改善COPD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
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财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Bacterial Infection in COPD
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批准号:8586872
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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
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批准号:8391088
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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
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批准号:8196313
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
-
负责人:Sanjay Sethi
-
依托单位:
Innate Immunity and exacerbations of COPD
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批准号:7008641
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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
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批准号:7471399
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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
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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
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批准号:7266876
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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