COMPLEMENT RECEPTORS--REGULATION OF EXPRESSION AND CELL BIOLOGY
COMPLEMENT RECEPTORS--REGULATION OF EXPRESSION AND CELL BIOLOGY
批准号:
3960586
负责人:
A MALBRAN
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
这项工作的目的是进一步确定生理机制。
调节补体和免疫球蛋白介导的吞噬作用。这
实验室以前曾研究过一些细胞事件,这些事件会导致
中性粒细胞或巨噬细胞能够通过CR1吞噬细胞,
补体成分C3的C3b片段的受体。在休息时
中性粒细胞,该受体不介导内化或
吞噬作用。然而,当中性粒细胞被佛波酯处理时,
CR1获得了两种新的活性:a)导致吞噬
C3b包裹的颗粒,以及b)连续的非配体依赖的内吞
进程。我们已经研究了CR1配体和内部受体的命运
佛波酯处理后的细胞。我们发现C3b CR1
复合体通过前溶酶体循环到细胞表面,
预酸性隔间,这个隔间与低
密度膜组件。然而,当CR1被交联时,
回收被减慢和减少,而另一个更大的隔间
展示了含有该配体的密度。未来的发展方向包括
该途径在细胞中的形态和动力学特征,
及其对Fc和CR1结合介导的吞噬功能的影响
感受器。
英文摘要
The objective of this work is to further define the physiologic mechanisms
that regulate complement and immunoglobulin mediated phagocytosis. This
laboratory has previously studied some of the cellular events that render a
polymorphonuclear leukocyte or macrophage able to phagocytose via CR1, the
receptor for the C3b fragment of the complement component C3. In resting
neutrophils, this receptor does not mediate internalization or
phagocytosis. However, when neutrophils are treated with phorbol esters,
CR1 acquires two new activities: a) the ability to cause phagocytosis of
C3b-coated particles, and b) a continuous and ligand-independent endocytic
process. We have studied the fate of CR1 ligands and the receptor inside
the cell following phorbol ester treatment. We have found that C3b CR1
complexes are recycled to the cell surface through a pre-lysosomal,
pre-acidic compartment and that this compartment is associated with a low
density membrane component. However, when CR1 is crosslinked, the
recycling is slowed and diminished, and a different compartment of greater
density containing the ligand is demonstrated. Future directions include
the morphologic and kinetic characterization of this pathway in the cell,
and its impact on phagocytosis mediated by a combination of Fc and CR1
receptors.
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