INTESTINAL GOBLET CELL FUNCTION
肠杯状细胞功能
基本信息
- 批准号:2139139
- 负责人:
- 金额:$ 11.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1984
- 资助国家:美国
- 起止时间:1984-04-01 至 1997-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The intestinal mucosa serves to absorb nutrients, solutes and fluid, but
simultaneously exclude luminal macromolecules and bacteria. The mucosal
barrier is composed of epithelial cells and their tight junctions;
failure of the mucosal barrier can lead to the dissemination of bacteria
and ultimately, multiple organ failure syndrome. Also protecting the
epithelium, is the mucus gel, composed of mucins, cellular debris, and
adherent IgA. Maintenance of the mucus gel is accomplished by the
baseline secretion of mucins from goblet cells. Numerous
pathophysiologic conditions, including cystic fibrosis and ulcerative
colitis, demonstrate altered mucin production/secretion; no physiologic
significance,, however, has been assigned to these phenomena. We propose
to characterize the role of mucins and an oxidant-generating enzyme of
goblet cell origin, intestinal peroxidase (IPO), in the pathogenesis of
ischemia/reperfusion (I/R), using the total occlusion of the superior
mesenteric artery as our model. First, we will determine the role of
luminal xanthine oxidase and IPO, as well as their oxidants, superoxide
anion radical and hypohalous acid, in the progression of mucosal injury,
using isotopic and morphological end-points. Second, we will
characterize the response of goblet cells to I/R-induced mucosal injury,
especially, the secretion of mucins and mucin species, as well as the
secretion of IPO. We will also determine the ability of mucins to
scavenge IPO-generated hypohalous acids to protect the epithelium.
Third, we will characterize the chemistry and physiology of IPO,
including: isolation and chemical composition; kinetic, bactericidal and
cytotoxic analysis; and the binding affinity of IPO to a reconstituted
mucin gel in vitro. Finally, we will use the information gained from the
characterization of mucins and IPO to attempt to interrupt the
pathogenesis of I/R-induced mucosal injury in vivo. Using the occlusion
of the SMA as a model, we will attempt to ameliorate mucosal damage by
inactivation of IPO activity with anti-IPO antibodies. We will also
attempt to scavenge reactive oxygen species in vivo with mucins.
Finally, we will attempt to mimic I/R -induced mucosal injury With
exogenous IPO and substrate. We hypothesize that the mucus gel is far
more versatile and bioactive than previously thought. That under normal
conditions, mucin-IPO interactions result in an antimicrobial-barrier in
the intestine, but that under conditions of ischemia/reperfusion, this
defense system results in the initiation of I/R-induced mucosal damage.
肠粘膜可吸收营养,溶质和液体,但
同时排除腔大分子和细菌。 粘膜
屏障由上皮细胞及其紧密连接组成。
粘膜屏障的失败会导致细菌的传播
最终,多器官衰竭综合征。 也保护
上皮是粘液凝胶,由粘蛋白,细胞碎片和
遵守IGA。 粘液凝胶的维护是由
从杯状细胞中粘蛋白的基线分泌。 很多的
病理生理状况,包括囊性纤维化和溃疡
结肠炎,表现出粘蛋白的产生/分泌改变;没有生理学
但是,意义已被分配给这些现象。 我们建议
表征粘蛋白和氧化剂生成酶的作用
杯状细胞起源,肠道过氧化物酶(IPO),在发病机理中
缺血/再灌注(I/R),使用上级的总阻塞
肠系膜动脉作为我们的模型。 首先,我们将确定
腔黄氨酸氧化酶和IPO及其氧化剂,超氧化物
阴离子自由基和低蓝酸,在粘膜损伤的进展中
使用同位素和形态学终点。 第二,我们会的
表征杯状细胞对I/R诱导的粘膜损伤的反应,
特别是,粘蛋白和粘蛋白物种的分泌以及
IPO的分泌。 我们还将确定粘蛋白的能力
清除IPO生成的低硅酸酸以保护上皮。
第三,我们将表征IPO的化学和生理学,
包括:隔离和化学组成;动力学,杀菌性和
细胞毒性分析; IPO与重构的绑定亲和力
体外粘蛋白凝胶。 最后,我们将使用从
粘蛋白和IPO的表征尝试中断
I/R诱导的体内粘膜损伤的发病机理。 使用阻塞
SMA作为模型,我们将尝试通过
使用抗IPO抗体的IPO活性灭活。 我们也会
试图用粘蛋白在体内清除活性氧。
最后,我们将尝试模仿I/R诱导的粘膜损伤
外源性IPO和底物。 我们假设粘液凝胶很远
比以前想象的更通用和生物活性。 在正常情况下
条件,粘蛋白-IPO相互作用导致在
肠,但在缺血/再灌注条件下,
防御系统会导致I/R诱导的粘膜损伤。
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)

暂无数据
数据更新时间:2024-06-01
ROBERT D SPECIAN的其他基金
CORE--MORPHOLOGY/IMAGING FACILITY
核心——形态学/成像设备
- 批准号:63447846344784
- 财政年份:2000
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
CORE--MORPHOLOGY/IMAGING FACILITY
核心——形态学/成像设备
- 批准号:62190206219020
- 财政年份:1999
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
CORE--MORPHOLOGY/IMAGING FACILITY
核心——形态学/成像设备
- 批准号:62707126270712
- 财政年份:1998
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
CORE--MORPHOLOGY/IMAGING FACILITY
核心——形态学/成像设备
- 批准号:61054786105478
- 财政年份:1998
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
CORE--MORPHOLOGY/IMAGING FACILITY
核心——形态学/成像设备
- 批准号:62390156239015
- 财政年份:1997
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
INTRACELLULAR MECHANICS OF INTESTINAL MUCUS SECRETION
肠粘液分泌的细胞内机制
- 批准号:31529153152915
- 财政年份:1984
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
INTRACELLULAR MECHANICS OF INTESTINAL MUCUS SECRETION
肠粘液分泌的细胞内机制
- 批准号:32321193232119
- 财政年份:1984
- 资助金额:$ 11.17万$ 11.17万
- 项目类别:
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