MODULATION OF LUNG ENDOTHELIAL PERMEABILITY BY AUTACOIDS
Autacoids 对肺内皮细胞通透性的调节
基本信息
- 批准号:3357790
- 负责人:
- 金额:$ 11.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-07-10 至 1994-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The measurement of blood-tissue permeability in the lung has
proven to be extremely difficult. We have developed a new in
vitro method to measure the permeability of cultured endothelial
cell layers from pulmonary arteries, veins, and microvessels. The
method offers a fresh approach and overcomes many of the
difficulties of whole animal methods used to study the increased
permeability edema often characteristic of the adult respiratory
distress syndrome. Blood-tissue permeability increases are
difficult to prove in animal models of increased permeability
edema. For example, investigators have such the sheep lung-
lymph preparation and stimuli such as histamine, endotoxin, and
thrombin as models of lung injury similar to increased
permeability edema. However, blood-tissue permeability changes
cannot be clearly identified in these animal models, since the lung
injury is accompanied by increased intravascular pressures which
could also account for the observed increased flux of fluid and
solutes. In vitro methods will help identify specific permeability
changes induced by agents producing lung injury in animals. Using
recent advances in cell culture methods, the permeability
characteristics of the endothelial component of the blood-tissue
barrier have begun to be investigated. However, these results are
being questioned, since these in vitro methods find permeabilities
1000 times greater than in vivo estimates.
In preliminary experiments, our in vitro method finds endothelial
permeabilities similar to in vivo estimates. This new method
utilizes a monolayer of endothelial cells cultured on microcarrier
beads as a selective barrier to control the passage of molecular
species from the mobile phase of a liquid chromatography column
to the stationary phase within the cell covered microcarrier
beads. We propose to use this method to clarify the role of the
endothelial barrier in blood-tissue permeability and, in addition,
measure how the permeability properties are altered by naturally
occurring stimuli, i.e. autacoids. This proposal has three main
aims: 1) to measure the in vitro intercellular permeability of the
pulmonary endothelial cell layer to mannitol and polyethylene
glycol; 2) to characterize the permeability of the pulmonary
endothelial cell layer with respect to tracer size and charge; and
3) to test the hypothesis that autacoids alter pulmonary
endothelial cell permeability by measuring permeability changes
produced by three autacoids, which have been described as
reversible modulators of blood-tissue permeability in the
lung: norepinephrine, thrombin and histamine.
测量肺部的血液组织渗透性
项目成果
期刊论文数量(4)
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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Frederick R Haselton其他文献
Frederick R Haselton的其他文献
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