REGULATION OF RESPIRATORY TRACT FLUID LAYERS
REGULATION OF RESPIRATORY TRACT FLUID LAYERS
批准号:
6109984
负责人:
Jonathan H Widdicombe
金额:
$11.7万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-09-01 至 1999-08-31
关键词:
Pseudomonas aeruginosa X ray spectrometry biological fluid transport bradykinin bronchial mucus chloride channels cystic fibrosis electrophysiology enzyme linked immunosorbent assay fluorescence microscopy hepatocyte growth factor histamine human tissue ion transport isoproterenol lactoferrin lysozyme membrane permeability methacholine radiotracer respiratory epithelium secretion sputum synthetic peptide tissue /cell culture
中文摘要
显微镜检查显示,呼吸道内的液体由两部分组成
层次感。睫毛周围有一层深度不等的粘液毯。
SOL,沐浴纤毛的一层透明的物质。环境污染的来源及治理
人们对这些层次的理解还不完全。然而,在囊性纤维化中,它
据认为,表面上皮细胞的异常离子运输改变了
水合作用这些层之间的关系或水合作用
粘液纤毛清除。在这个提案中,我们将检验两个假设。
首先,我们认为表面上皮细胞的离子转运是
在调节睫毛周围溶胶的深度方面几乎不重要,这是
通过毛细的力量精确地设定在纤毛的长度
由大的组合圆周长度(每平方厘米600米)产生
纤毛的表面)。其次,我们提出了有缺陷的客户关系
而腺体分泌的液体主要负责最初的
囊性纤维化中粘液堆积。这些缺陷导致了
脱水的粘液不会从腺体开口完全分离
和/或不会有效地被纤毛运输。此外
腺体中CFTR的故障可能会改变硫酸盐化或其他特性
腺体粘液,再次损害粘液纤毛清除。为了测试这些
假设,我们将研究渗透和活性液体如何流过
表面上皮改变粘液层的深度,以及这些
变化会影响粘液的运输。流体层将在中可视化
扫描电子显微镜下快速冷冻组织的横切面
显微镜。我们将测量介体诱导的体液分泌跨CF和
使用电容探针技术的非CF细胞培养,并从完整
用微吸管从导管开口取样腺体。我们将确定是否
从CF腺和表面培养物中提取的粘蛋白的硫酸盐化和流变学
不正常。最后,我们将确定本地化和总级别
CFTR在我们的文化中存在,并与激素诱导的
这些参数随功能的变化而变化。其中大部分建议
实验将在我们最近开发的原代培养物上进行
表面和腺体上皮,显示出高水平的超微结构
和功能分化。
英文摘要
Microscopy has shown the fluid lining the airways to consist of two
layers. A mucous blanket of variable depth lies on top of the periciliary
sol, a clear layer which bathes the cilia. The sources and regulation of
these layers are incompletely understood. However, in cystic fibrosis, it
is believed that abnormal ion transport by the surface epithelium alters
the relationship or hydration of these layers in such a way as to impair
mucociliary clearance. In this proposal we will test two hypotheses.
Firstly, we suggest that ion transport by the surface epithelium is of
little importance in regulating the depth of the periciliary sol, which is
set precisely at the length of the cilia by forces of capillarity
generated by the large combined circumferential length (600 m per cm2 of
epithelial surface) of the cilia. Secondly, we propose that defective Cl
and fluid secretion by the glands is mainly responsible for the initial
accumulation of mucus in cystic fibrosis. These defects result in
dehydrated mucus which will not detach fully from the gland openings
and/or will not be effectively transported by the cilia. In addition
malfunction of CFTR in glands may alter the sulfation or other properties
of gland mucus, again impairing mucociliary clearance. To test these
hypotheses, we will investigate how osmotic and active fluid flows across
the surface epithelium alter the depth of the mucus layers, and how these
changes affect mucus transport. The fluid layers will be visualized in
transverse sections of rapidly frozen tissues in the Scanning electron
microscope. We will measure mediator-induced fluid secretion across CF and
non-CF cell cultures using a capacitance probe technique, and from intact
glands by micropipette sampling from duct openings. We will determine if
the sulfation and rheology of mucins from CF gland and surface cultures is
abnormal. Finally, we will determine the localization and total levels of
CFTR in our cultures, and correlate hormonally-induced alterations in
these parameters with changes in function. Most of these proposed
experiments will be performed on our recently developed primary cultures
of surface and gland epithelia, which show high levels of ultrastructural
and functional differentiation.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
LOW TEMPERATURE SEM AND X RAY MICROANALYSIS OF ASL
-
批准号:6354737
-
项目类别:
-
资助金额:$18.09万
-
财政年份:2000
-
负责人:Jonathan H Widdicombe
-
依托单位:
ENDOGENOUS ANTIBIOTICS IN NASAL LAVAGE
-
批准号:6308609
-
项目类别:
-
资助金额:$1.75万
-
财政年份:1999
-
负责人:Jonathan H Widdicombe
-
依托单位:
LOW TEMPERATURE SEM AND X RAY MICROANALYSIS OF ASL
-
批准号:6202599
-
项目类别:
-
资助金额:$18.09万
-
财政年份:1999
-
负责人:Jonathan H Widdicombe
-
依托单位:
ALTERATIONS IN AIRWAY SURFACE LIQUID IN CYSTIC FIBROSIS
-
批准号:6389917
-
项目类别:
-
资助金额:$94.67万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
ALTERATIONS IN AIRWAY SURFACE LIQUID IN CYSTIC FIBROSIS
-
批准号:6056520
-
项目类别:
-
资助金额:$89.48万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
ALTERATIONS IN AIRWAY SURFACE LIQUID IN CYSTIC FIBROSIS
-
批准号:2621743
-
项目类别:
-
资助金额:$90.46万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
ALTERATIONS IN AIRWAY SURFACE LIQUID IN CYSTIC FIBROSIS
-
批准号:6184475
-
项目类别:
-
资助金额:$92.04万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
LOW TEMPERATURE SEM AND X RAY MICROANALYSIS OF ASL
-
批准号:6110946
-
项目类别:
-
资助金额:$18.09万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
ALTERATIONS IN AIRWAY SURFACE LIQUID IN CYSTIC FIBROSIS
-
批准号:6527149
-
项目类别:
-
资助金额:$95.43万
-
财政年份:1998
-
负责人:Jonathan H Widdicombe
-
依托单位:
CORE--CELL BIOLOGY LABORATORY
-
批准号:6105620
-
项目类别:
-
资助金额:$5.2万
-
财政年份:1997
-
负责人:Jonathan H Widdicombe
-
依托单位:
CFTR AND AIRWAY PATHOLOGY OF CYSTIC FIBROSIS
-
批准号:2220436
-
项目类别:
-
资助金额:$51.08万
-
财政年份:1993
-
负责人:Jonathan H Widdicombe
-
依托单位:
CFTR AND AIRWAY PATHOLOGY OF CYSTIC FIBROSIS
-
批准号:2028450
-
项目类别:
-
资助金额:$60.03万
-
财政年份:1993
-
负责人:Jonathan H Widdicombe
-
依托单位:
CFTR AND AIRWAY PATHOLOGY OF CYSTIC FIBROSIS
-
批准号:3106855
-
项目类别:
-
资助金额:$51.0万
-
财政年份:1993
-
负责人:Jonathan H Widdicombe
-
依托单位:
CFTR AND AIRWAY PATHOLOGY OF CYSTIC FIBROSIS
-
批准号:2519306
-
项目类别:
-
资助金额:$58.51万
-
财政年份:1993
-
负责人:Jonathan H Widdicombe
-
依托单位:
CFTR AND AIRWAY PATHOLOGY OF CYSTIC FIBROSIS
-
批准号:2220435
-
项目类别:
-
资助金额:$50.08万
-
财政年份:1993
-
负责人:Jonathan H Widdicombe
-
依托单位:
PROTEIN PHOSPHORYLATION AND AIRWAY CHLORIDE SECRETION
-
批准号:3239604
-
项目类别:
-
资助金额:$10.52万
-
财政年份:1988
-
负责人:Jonathan H Widdicombe
-
依托单位:
REGULATION OF APICAL MEMBRANE CL CHANNELS IN AIRWAYS
-
批准号:3106856
-
项目类别:
-
资助金额:$67.93万
-
财政年份:1988
-
负责人:Jonathan H Widdicombe
-
依托单位:
REGULATION OF APICAL MEMBRANE CL CHANNELS IN AIRWAYS
-
批准号:3106859
-
项目类别:
-
资助金额:$59.84万
-
财政年份:1988
-
负责人:Jonathan H Widdicombe
-
依托单位:
PROTEIN PHOSPHORYLATION AND AIRWAY CHLORIDE SECRETION
-
批准号:3239603
-
项目类别:
-
资助金额:$8.89万
-
财政年份:1988
-
负责人:Jonathan H Widdicombe
-
依托单位:
PROTEIN PHOSPHORYLATION AND AIRWAY CHLORIDE SECRETION
-
批准号:3239602
-
项目类别:
-
资助金额:$6.78万
-
财政年份:1988
-
负责人:Jonathan H Widdicombe
-
依托单位:
海外基金