Investigation of human mast cell biological function induced by FcγRI aggregation

我们曾报道人肥大细胞表达一种功能性的高亲和力免疫球蛋白G受体FeγRI，并且其表达被干扰素-γ上调(J免疫杂志，2000,164：4332)。在FcγRI聚集后，人肥大细胞释放和合成组胺和脂类介质，并产生多种细胞因子，特别是促炎细胞因子，如肿瘤坏死因子-α和IL-1β(J免疫学杂志，2001,166：4705；欧洲免疫学杂志，2001，31：3298)。我们检测了FcγRI依赖的特定信号转导分子的激活，并确定了这些事件在FcαRI和FcγRI聚集后对人肥大细胞脱颗粒和肿瘤坏死因子-ε的产生的相对参与。人肥大细胞中FCγRI聚集后的信号事件与FCεRI聚集后观察到的信号事件大致相似。一个例外是，尽管磷脂酰肌醇-3-激酶在FcεRI和FcγRI聚集后都被激活，但似乎只有FcγRI需要该分子来脱颗粒(Okayama Y，等人)。欧盟免疫学杂志，2003，33,1450。此外，我们还证明了预先形成的肥大细胞相关的肿瘤坏死因子-α的释放作为一个正的自分泌反馈信号来增强核因子-kB的激活和进一步的细胞因子的产生，包括GM-CSF和IL-8(J免疫学杂志，2002,169：5287)。为了系统地探讨人肥大细胞在FcεRI和FcγRI聚集后如何调节免疫系统，我们使用高密度寡核苷酸探针阵列比较了肥大细胞中Ig E/抗Ig E诱导的基因表达谱和Ig G1Ant-Ig G1I介导的基因表达谱。两种表达谱相似，但鉴定了FcγRI聚集介导的特异性基因表达谱(Okayama Y，等人)。正在准备中)。我们还发现干扰素-γ上调了Toll样受体4(TLR4)的表达(Okumura S等)。布拉德，2003,102：2547)。这些发现表明，在人肥大细胞上表达的FcγRI在Th1环境中具有与FcεRI不同的生理和病理功能。

We have previously reported that human mast cells express a functional high affinity IgG receptor, FeγRI and its expression is up-regulated by IFN-γ(J Immunol,2000,164:4332). Following FcγRI aggregation, human mast cells release and synthesize histamine and lipd mediators, and also produce a various cytokines, especially proinflammatory cytokines such as TNF-α and IL-1β(J Immunol,2001,166:4705,Eur J Immunol,2001,31:3298). We examined FcγRI -dependent activation of specific signal transduction molecules and determined the relative involvement of these events in human mast cell degranulation and TNF-α production following both FcγRI and FcεRI aggregation. Signaling events in human mast cells following aggregation of FcγRI were generally similar to those observed following FcεRI aggregation. The one exception was that, although phosphatidylinositol-3-kinase was activated after both FcεRI and FcγRI aggregation, only the FcγRI appeared to require this molecule for degranulation (Okayama Y, et al. Eur J Immunol,2003,33,1450. Furthermore, we demonstrated that the release of preformed mast cell-associated TNF-a acts as a positive autocrine feedback signal to augment NF-kB activation and production of further cytokine, including GM-CSF and IL-8 (J Immunol,2002,169:5287). To systematically explore how human mast cells modulate immune system following FcεRI and FcγRI aggregation, we used high-density oligonucleotide probe arrays to compare the IgE/anti-IgE-induced gene expression profile with IgG1/ant-IgG1-mediated profile in mast cells. Both expression profiles were similar, but specific gene expression profile mediated by FcγRI aggregation was identified (Okayama Y, et al. in preparation). We also found that a functional Toll-like receptor 4 (TLR4) was up-regulated by IFN-γ(Okumura S, et al. Blood,2003,102:2547). These findings suggest that FcγRI expressed on human mast cells, appears to have different physiological and pathlogical function in Th1 environment from FcεRI.