van Egmond M, Hanneke van Vuuren A J, van de Winkel J G
Department of Immunology, University Medical Centre Utrecht, The Netherlands.
Immunol Lett. 1999 May 3;68(1):83-7. doi: 10.1016/s0165-2478(99)00034-6.
Even though IgA is considered to play an important role in immunity, surprisingly little is known about the presence of IgA Fc receptor (Fc alpha R)-expressing effector cells in tissues. Difficulties in obtaining human tissue macrophages, led us to study peritoneal macrophages in a human Fc alpha RI transgenic (Tg) mouse model. Naive peritoneal macrophages did not express hFc alpha RI. Expression, however, could be induced by overnight culture, and was upregulated by GM-CSF. In addition, the receptor proved functional since macrophage-mediated phagocytosis and tumor cell kill were effectively triggered via hFc alpha RI. To assess necessity of the FcR gamma-chain signaling molecule for hFc alpha RI function in macrophages, Tg mice were crossed with mice deficient in FcR gamma-chain (gamma-/-). Tg, gamma-/- macrophages were unable to kill tumor cells. This, because Tg macrophages failed to express hFc alpha RI in the absence of FcR gamma-chain, and overnight culture did not overcome this lack of expression. Further studies with the transgenic mouse model presented in this study will help to define the precise conditions under which Fc alpha RI is expressed on macrophages. It will, furthermore, represent a useful tool to study Fc alpha RI function in immune defense.
尽管IgA被认为在免疫中发挥重要作用，但令人惊讶的是，对于组织中表达IgA Fc受体（FcαR）的效应细胞的存在了解甚少。获取人类组织巨噬细胞存在困难，这促使我们在人类FcαRI转基因（Tg）小鼠模型中研究腹膜巨噬细胞。未活化的腹膜巨噬细胞不表达人FcαRI。然而，通过过夜培养可诱导其表达，且GM-CSF可使其表达上调。此外，该受体被证明具有功能，因为巨噬细胞介导的吞噬作用和肿瘤细胞杀伤可通过hFcαRI有效触发。为了评估FcRγ链信号分子对巨噬细胞中hFcαRI功能的必要性，将Tg小鼠与FcRγ链缺陷（γ-/-）的小鼠杂交。Tg、γ-/-巨噬细胞无法杀伤肿瘤细胞。这是因为在没有FcRγ链的情况下，Tg巨噬细胞无法表达hFcαRI，过夜培养也无法克服这种表达缺失。对本研究中提出的转基因小鼠模型的进一步研究将有助于确定巨噬细胞上表达FcαRI的精确条件。此外，它将成为研究FcαRI在免疫防御中功能的有用工具。
