CD14 AND LPS-INDUCED INFLAMMATION IN CHRONIC BRONCHITIS
CD14 AND LPS-INDUCED INFLAMMATION IN CHRONIC BRONCHITIS
批准号:
6285821
负责人:
David B. Peden
金额:
$32.65万
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:
CD14 molecule alveolar macrophages apoptosis chronic bronchitis chronic obstructive pulmonary disease clinical research enzyme linked immunosorbent assay flow cytometry genetic susceptibility genotype human subject immunofluorescence technique immunologic assay /test inflammation lipopolysaccharides nitric oxide pathologic process radioimmunoassay receptor binding receptor expression respiratory gas analyzer smoking spirometry tobacco abuse
中文摘要
描述(改编自申请人的摘要)
慢性支气管炎和慢性阻塞性肺疾病的特征是慢性中性粒细胞
炎症,并与革兰氏阴性的两种呼吸道败血症相关
细菌。吸烟是罹患这些疾病的主要危险因素,
但只有大约20%的吸烟者会患上慢性阻塞性肺疾病。内毒素(ET)来自革兰氏
负性细菌可能在这种炎症中起着重要作用。气道口
内毒素可能直接来自感染呼吸道的革兰氏阴性细菌或来自
烟草烟雾,因为这是ET的另一个丰富来源。调查人员建议
对ET的反应性也是发展为
吸烟者的慢性阻塞性肺疾病。人们可能对ET更敏感的一种机制
是通过增强ET的主要受体CD14的产生来实现的。CD14存在
以细胞结合形式和以可溶性形式存在于血清和呼吸道中
分泌物。急性变态反应引起呼吸道中可溶性CD14的升高
发炎。此外,还发现了C/T多态。
CD14启动子基因(CD14基因)159位。那些纯合的人
因为T等位基因已经被证明增加了血清中可溶性CD14和
CD14在外周血单核细胞上的表达与CT或CC基因型的比较。
调查人员提供的初步数据表明,
激发前痰中sCD14和肺泡巨噬细胞CD14的表达
内毒素(内毒素)与中性粒细胞内流相关
在吸入内毒素激发后的痰中。此外,在鼻腔内,
变应原增强粒细胞对内毒素的反应
与当地的sCD14水平。
研究人员建议研究CD14在确定
吸烟者对呼吸道内毒素的反应性和患COPD的风险。首先,
研究人员将确定巨噬细胞上的sCD14和CD14水平是否
在实验诱导和自然发生的志愿者中增加
支气管炎和中性粒细胞对内毒素的反应是否增加。第二,
研究人员确定呼吸道CD14是否与中性粒细胞对内毒素的反应有关
正常的志愿者。第三,调查人员将确定呼吸道CD14是否
携带TT型的健康志愿者的水平和内毒素反应
CD14基因相对CC、CT等位基因有增强作用。
最后,研究人员将对COPD患者和健康人群进行基因分型
吸烟者确定T等位基因是否为慢性阻塞性肺疾病发病的危险因素
在那些吸烟的人身上。
英文摘要
DESCRIPTION (adapted from the applicants' abstract)
Chronic bronchitis and COPD are characterized by chronic neutrophilic
inflammation and is associated with both airway sepsis with gram-negative
bacteria. Smoking is a major risk factor for development of these diseases,
but only about 20 percent of smokers develop COPD. Endotoxin (ET) from gram-
negative bacteria likely plays a significant role in this inflammation. Airway
ET may come directly from gram-negative bacteria infecting the airway or from
tobacco smoke as this is another rich source of ET. The investigators propose
that responsiveness to ET also an important risk factor for development of
COPD in smokers. One mechanism by which persons may be more sensitive to ET
is by enhanced production of CD14, the primary receptor for ET. CD14 exists
in both a cell bound form and as a soluble from in serum and airway
secretions. Soluble CD14 in the airway is enhanced by acute allergic
inflammation. Additionally, a C/T polymorphism has been identified at the -
159 position of the CD14 promoter gene (CD14 gene). Those persons homozygous
for the T allele have been shown to have increased soluble CD14 in serum and
CD14 expression on blood monocytes compared to those with CT or CC genotype.
The investigators present preliminary data that demonstrates that levels of
sCD14 in sputum and CD14 expression on alveolar macrophages prior to challenge
with lipopolysacharride (LPS, a form of ET) correlates with neutrophil influx
in sputum following inhaled LPS challenge. Also, in the nasal airway,
allergen enhances granulocyte response to LPS in a fashion which correlates
with local sCD14 levels.
The investigators propose to examine the role that CD14 has in determining
responsiveness to airway LPS and risk for COPD in smokers. First, the
investigators will determine if the level of sCD14 and CD14 on macrophages is
increased in volunteers with experimentally-induced and naturally occurring
bronchitis and if they have increased neutrophil response to LPS. Second, the
investigators determine if airway CD14 correlates with PMN response to LPS in
normal volunteers. Third, the investigators will determine if airway CD14
levels and LPS response in healthy volunteers with the TT genotype for the
CD14 gene is enhanced relative to that in those with the CC and CT genotype.
Finally, the investigators will genotype cohorts of COPD patients and healthy
smokers to determine if the T allele is a risk factor in development of COPD
in those who smoke.
期刊论文(0)
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科研奖励(0)
会议论文
Research Training in Allergy and Clinical Immunology
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批准号:10493540
-
项目类别:
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资助金额:$42.43万
-
财政年份:2022
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负责人:David B. Peden
-
依托单位:
Research Training in Allergy and Clinical Immunology
-
批准号:10686797
-
项目类别:
-
资助金额:$44.39万
-
财政年份:2022
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负责人:David B. Peden
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依托单位:
Project 4: Treatment of mucostasis and airways obstruction in asthma with a novel mucolytic
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批准号:10001602
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项目类别:
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资助金额:$34.72万
-
财政年份:2017
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负责人:David B. Peden
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依托单位:
Project 4: Treatment of mucostasis and airways obstruction in asthma with a novel mucolytic
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批准号:9356821
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项目类别:
-
资助金额:$34.93万
-
财政年份:2017
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负责人:David B. Peden
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依托单位:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
-
批准号:9222012
-
项目类别:
-
资助金额:$55.5万
-
财政年份:2016
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负责人:David B. Peden
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依托单位:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
-
批准号:9883794
-
项目类别:
-
资助金额:$55.5万
-
财政年份:2016
-
负责人:David B. Peden
-
依托单位:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
-
批准号:9055845
-
项目类别:
-
资助金额:$58.08万
-
财政年份:2016
-
负责人:David B. Peden
-
依托单位:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
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批准号:9269215
-
项目类别:
-
资助金额:$87.41万
-
财政年份:2013
-
负责人:David B. Peden
-
依托单位:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
-
批准号:8598698
-
项目类别:
-
资助金额:$52.61万
-
财政年份:2013
-
负责人:David B. Peden
-
依托单位:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
-
批准号:8733697
-
项目类别:
-
资助金额:$51.52万
-
财政年份:2013
-
负责人:David B. Peden
-
依托单位:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
-
批准号:9057036
-
项目类别:
-
资助金额:$87.73万
-
财政年份:2013
-
负责人:David B. Peden
-
依托单位:
Investigating gene x environment interaction using human exposures to O3 & LPS
-
批准号:7829058
-
项目类别:
-
资助金额:$48.4万
-
财政年份:2009
-
负责人:David B. Peden
-
依托单位:
Investigating gene x environment interaction using human exposures to O3 & LPS
-
批准号:7939789
-
项目类别:
-
资助金额:$49.28万
-
财政年份:2009
-
负责人:David B. Peden
-
依托单位:
Immunobiology of Acute Environmental Asthma
-
批准号:7901225
-
项目类别:
-
资助金额:$85.2万
-
财政年份:2009
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负责人:David B. Peden
-
依托单位:
Administrative Core
-
批准号:7977212
-
项目类别:
-
资助金额:$14.32万
-
财政年份:2009
-
负责人:David B. Peden
-
依托单位:
Airway Biology of Acute Environmental Asthma in Humans
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批准号:7977203
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项目类别:
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资助金额:$37.72万
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财政年份:2009
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负责人:David B. Peden
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依托单位:
Immunobiology of Acute Environmental Asthma
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批准号:7763809
-
项目类别:
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资助金额:$180.72万
-
财政年份:2008
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负责人:David B. Peden
-
依托单位:
Airway Biology of Acute Environmental Asthma in Humans
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批准号:7476119
-
项目类别:
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资助金额:$36.74万
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财政年份:2008
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负责人:David B. Peden
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依托单位:
Immunobiology of Acute Environmental Asthma
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批准号:8636628
-
项目类别:
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资助金额:$18.61万
-
财政年份:2008
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负责人:David B. Peden
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依托单位:
Immunobiology of Acute Environmental Asthma
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批准号:7426009
-
项目类别:
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资助金额:$150.41万
-
财政年份:2008
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负责人:David B. Peden
-
依托单位:
海外基金