COMPLEMENT RECEPTORS--REGULATION OF EXPRESSION AND CELL BIOLOGY

补体受体——表达和细胞生物学的调节

• 批准号: 3960586
• 负责人: A MALBRAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960586
• 关键词: calcium; cell biology; complement; complement pathway; diacylglycerols; immunoregulation; macrophage; monoclonal antibody; neutrophil; opsonin; phagocytes; phagocytosis; phorbols; phosphatidylinositols; protein kinase C; receptor mediated endocytosis

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.

这项工作的目的是进一步确定的生理机制 调节补体和免疫球蛋白介导的吞噬作用。 这 一个实验室先前研究了一些细胞事件， 多形核白细胞或巨噬细胞能够通过CR 1吞噬， 补体成分C3的C3 b片段的受体。 静息 中性粒细胞，该受体不介导内化或 吞噬作用 然而，当中性粒细胞用佛波醇酯处理时， CR 1获得了两种新的活性：a）引起吞噬细胞的能力， C3 b-包被的颗粒，和B）连续的和配体非依赖性的内吞 过程 我们已经研究了CR 1配体和受体的命运， 佛波醇酯处理后的细胞。 我们发现C3 b CR 1 复合物通过前溶酶体再循环到细胞表面， 前酸隔室，该隔室与低 密度膜组件。 然而，当CR 1交联时， 再循环减慢和减少，不同的隔间更大， 证明了含有配体的密度。 未来的方向包括 细胞中该途径的形态学和动力学特征， 及其对Fc和CR 1组合介导的吞噬作用的影响 受体。