AIRWAY MYOCYTE PROLIFERATION & LYSOSOMAL HYDROLASE
气道心肌细胞增殖
基本信息
- 批准号:3473615
- 负责人:
- 金额:$ 9.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-08-01 至 1996-07-31
- 项目状态:已结题
- 来源:
- 关键词:adenylate cyclase asthma beta N acetylhexosaminidase binding proteins calcium carbohydrate receptor cell differentiation cow cyclic AMP diacylglycerols enzyme inhibitors enzyme mechanism fluorescent dye /probe glycoproteins hyperplasia inhibitor /antagonist mannose mitogens muscle cells prostaglandin E protein kinase C radioimmunoassay radiotracer respiratory hypersensitivity smooth muscle tissue /cell culture trachea
项目摘要
Smooth muscle hyperplasia/hypertrophy is a well recognized pathological
change of asthma and may play an important role in the development of
airway hyperreactivity, the hallmark of asthma. Lysosomal hydrolases,
secretory products of inflammatory cells, are implicated in pathogenesis of
allergen-induced asthma and ozone-induced muscarinic hyperreactivity. The
proposed study is based on our preliminary findings of a potent mitogenic
action of purified lysosomal hydrolases (hexosaminidases) on bovine
tracheal airway myocyte by lysosomal hydrolases. The objective of this
proposal is to investigate the mechanism(s) involved in airway myocyte
proliferation induced by lysosomal hydrolases. Specific aims are 1) To
determine if a receptor-ligand interaction (specifically mannose receptor)
is required for the mitogenic action of hydrolases. 2) To investigate
whether arachidonic acid metabolites, particularly prostaglandin E2 (PGE2)
is a mediator of lysosomal hydrolase induced mitogenesis. 3) To
investigate whether or not mitogenic action of hydrolases is mediated
through the activation of adenylate cyclase. 4) To explore a possible
contribution of protein kinase C (PKC) and diacylglycerol (DAG) in the
mitogenic effects of lysosomal hydrolases. 5) To establish the role
cytosolic calcium in the mitogenic effects of lysosomal hydrolases. To
accomplish specific aim 1: a) The presence of mannose receptor on bovine
tracheal myocytes will be documented by antibody recognition and receptor
type(s) will be characterized. Iodinated glycoproteins will be used for
binding study and mannan and fructose-1-phosphate will be used for
competition of binding. b) We will examine the effect of blocking
receptor-ligand interaction. Receptor inhibitors and blockers will be
utilized and their effect will be correlated to 3H-thymidine (TdR)
incorporation induced by lysosomal hydrolases. c) Possible internalization
of lysosomal hydrolases as a requirement in mitogenic action will be
studied. Inhibitors of mannose receptor and agarose and sepharose bound
hydrolases will be applied to inhibit internalization. For aims 2, 3, 4,
and 5, changes of PGE2 production, cAMP level, DAG level, PKC activity,
cytosolic [Ca++] and inositol-triphosphate (IP3) levels; respectively will
be studied in the presence and the absence of lysosomal hydrolases.
Inhibitors and activators of second messenger systems and cyclooxygenase
will be tested for their effects on mitogenesis induced by lysosomal
hydrolases. Intracellular cAMP levels and PGE2 production will be measured
by RIA and cytosolic calcium will be measured using Fura 2 fluorescent
indicator. [32P] ATP, phosphatidyl serine and Histone IIIS will be used to
assay PKC activity. Above measurements will be correlated to 3H-TdR
incorporation. Understanding the receptor-dependent and the receptor-
independent mechanism(s) of lysosomal hydrolase-induced airway myocyte
proliferation would allow us to develop a method of prevention of smooth
muscle hyperplasia/hypertrophy seen in asthma.
平滑肌增生/肥大是一种公认的病理
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DUKHEE Betty LEW其他文献
DUKHEE Betty LEW的其他文献
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{{ truncateString('DUKHEE Betty LEW', 18)}}的其他基金
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
6351498 - 财政年份:1998
- 资助金额:
$ 9.88万 - 项目类别:
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
2872945 - 财政年份:1998
- 资助金额:
$ 9.88万 - 项目类别:
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
2468206 - 财政年份:1998
- 资助金额:
$ 9.88万 - 项目类别:
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
6151334 - 财政年份:1998
- 资助金额:
$ 9.88万 - 项目类别:
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
2223336 - 财政年份:1991
- 资助金额:
$ 9.88万 - 项目类别:
AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
气道肌细胞增殖和溶酶体水解酶
- 批准号:
2223335 - 财政年份:1991
- 资助金额:
$ 9.88万 - 项目类别:
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