Molecular analysis of expression and function of hFcγRIIbl and b2 isoforms in myeloid cells
- 作者：Trupti Joshi ; Latha P. Ganesan ; Xianhua Cao and Susheela Tridandapani
- 关键词：Fcγ ; receptors ; Phagocytosis ; ITIM ; Negative regulation ; Signal transduction
- 刊名：Molecular Immunology
- 出版年：2006
- 期刊代码：112_01615890
- 类别：bio
- 出版时间：March 2006
- 卷：43
- 期：7
- 页码：839-850
- 文件大小：477 K
摘要
The inhibitory receptor FcγRIIb becomes tyrosine phosphorylated and associates with the inositol phosphatase SHIP to downregulate phagocytosis. The two splice variants of FcγRIIb, b1 and b2, are differentially expressed in hematopoetic cells. Both isoforms of FcγRIIb are expressed in human myeloid cells although FcγRIIb2 predominates. In murine B cells FcγRIIb2 associates with clathrin-coated pits and undergoes endocytosis, whereas FcγRIIbl is excluded from the coated pits, indicating that the two isoforms serve partially differing functions. In humans, there are conflicting reports with regard to the ability of FcγRIIb2 to become tyrosine phosphorylated, and the functional capacities of the two isoforms are poorly understood. We, and others, have previously reported that the expression of FcγRIIb is upregulated in human monocytes by the anti-inflammatory cytokine IL-4. Here, we extend these findings to demonstrate that the IL-4-induced upregulation of FcγRIIb is synergistically enhanced by the addition of IL-10, both at the protein and the mRNA level. The upregulated receptors are functional as assessed by their ability to become tyrosine phosphorylated and to downregulate phagocytosis. Interestingly, both b1 and b2 isoforms are upregulated by anti-inflammatory cytokines. Transfection experiments expressing human FcγRIIbl or b2 in Raw 264.7 murine macrophage cells revealed that both isoforms are tyrosine phosphorylated and promote SHIP phosphorylation. Finally, both b1 and b2 isoforms of FcγRIIb downregulate phagocytosis to a similar extent. Thus we conclude that FcγRIIbl and b2 are both functional inhibitory receptors in the phagocytic process.