Structure/function relationships of Fc gamma receptors in phagocytosis.
Structure/function relationships of Fc gamma receptors in phagocytosis.
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DOI：
10.1016/1044-5323(95)90007-1
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发表时间：
1995-02-01
影响因子：
7.8
通讯作者：
Schreiber, A D
中科院分区：
文献类型：
--
作者：
Indik, Z K;Park, J G;Schreiber, A D
Fc γ受体的一个重要功能是摄取或吞噬IgG致敏细胞。由于造血细胞表达多种Fc γ受体亚型，因此很难明确定义每种受体在吞噬中的单独功能。为了研究这个问题，我们开发了COS-1细胞的体外模型系统。当转染适当的Fc受体时，缺乏内源性Fc受体的COS-1细胞摄取igg致敏细胞。利用该模型，我们观察到在缺乏其他Fc受体的情况下，一类人Fc γ受体介导吞噬作用。此外，尽管对吞噬作用的要求不同，但来自每种Fc γ受体类的同种异构体都可以介导吞噬作用。对Fc受体介导的吞噬作用的结构和功能之间关系的研究确立了受体或其相关γ链的细胞质酪氨酸的重要性。例如，两个细胞质YXXL序列，其结构类似于免疫球蛋白基因家族受体中含有保守酪氨酸基序的结构，对人类Fc γ受体Fc γ RIIA的吞噬作用很重要。Fc γ RI和Fc γ RIIIA不具有细胞质酪氨酸，但通过与相关γ -亚基相互作用传递吞噬信号，该亚基包含吞噬所需的保守基序中的两个YXXL序列。人类Fc γ RII亚型Fc γ RIIB2不诱导吞噬，只有一个单一的YXXL序列。吞噬Fc γ受体的交联可诱导Fc γ RIIA或γ链的酪氨酸磷酸化，酪氨酸激酶抑制剂可减少吞噬作用和受体酪氨酸残基的磷酸化。与单核/巨噬细胞γ链相关的蛋白酪氨酸激酶Syk可显著增强Fc γ RI和Fc γ RIIIA介导的吞噬作用，并诱导表达Fc γ RI或Fc γ RIIIA的非吞噬细胞获得吞噬能力。
An important function of Fc gamma receptors is the ingestion or phagocytosis of IgG sensitized cells. It has been difficult to clearly define the individual function of each receptor in phagocytosis because hematopoietic cells express multiple Fc gamma receptor isoforms. To examine this issue, an in-vitro model system in COS-1 cells has been developed. When transfected with an appropriate Fc gamma receptor, COS-1 cells which lack endogeneous Fc receptors, ingest IgG-sensitized cells. Using this model, a single class of human Fc gamma receptor in the absence of other Fc receptors was observed to mediate phagocytosis. Furthermore, isoforms from each Fc gamma receptor class can mediate phagocytosis although the requirements for phagocytosis differ. Investigation of the relationship between structure and function for Fc receptor-mediated phagocytosis established the importance of the cytoplasmic tyrosines of the receptor or its associated gamma chains. For example, two cytoplasmic YXXL sequences, in a configuration similar to the conserved tyrosine containing motif found in immunoglobulin gene family receptors, are important for phagocytosis by the human Fc gamma receptor, Fc gamma RIIA. Fc gamma RI and Fc gamma RIIIA do not possess cytoplasmic tyrosines, but transmit a phagocytic signal through interaction with an associated gamma-subunit which contains two YXXL sequences in a conserved motif required for phagocytosis. The human Fc gamma RII isoforms, Fc gamma RIIB2, do not induce phagocytosis and have only a single YXXL sequence. Crosslinking of the phagocytic Fc gamma receptors induces tyrosine phosphorylation of either Fc gamma RIIA or the gamma chain and treatment with tyrosine kinase inhibitors reduces both phagocytosis and phosphorylation of the receptor tyrosine residues. The protein tyrosine kinase Syk, which is associated with the gamma chain in monocytes/macrophages, dramatically enhances phagocytosis mediated by Fc gamma RI and Fc gamma RIIIA and also induces non-phagocytic Fc gamma RI or Fc gamma RIIIA expressing cells to acquire phagocytic capability.