Analysis of expression mechanism of FcepsilonRI on human mast cells.

FcepsilonRI在人肥大细胞上的表达机制分析。

• 批准号: 08670860
• 负责人: NONOYAMA Shigeaki
• 金额: $ 1.47万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670860/
• 关键词: Mast cells; FcepsilonRI; IL-4; Allergy

Recently, we have established a culture system of human mast cells derived from cord blood mononuclear cells in the presence of stem cell factor (SCF) and IL-6. More than 99% of the cultured cells express c-kit antigen and contain tryptase and histamine, indicating that these cultured cells posses the typical features of mast cells. This culture system provides us with an excellent model to study the effect of cytokines on human mast cells.Here we report that IL-4 induces FcepsilonRl expression on human mast cells resulting in high histamine release. We also found that IL-4 promotes the growth of the cultured human mast cells as well as the increased expression of LFA- 1 and ICAM- 1 causing homotypic aggregation of the cells. These results demonstrate that IL-4 is a potent activating factor for human mast cells and may play an important role in the allergic reaction caused by mast cells. Since IL-4 is produced in increased amounts by T cells of patients with allergic disorders, mast cells of allergic individuals may be in a constant hyper-reactive state and contribute to all processes of allergic inflammation. The signal transduction pathway of the IL-4 on the activation of mast cells, which is likely to be regulated in transcriptional level, is now on study.

最近，我们已经建立了一个培养系统的人肥大细胞来源于脐血单个核细胞在干细胞因子（SCF）和IL-6的存在。99%以上的培养细胞表达c-kit抗原，并含有类胰蛋白酶和组胺，表明这些培养细胞具有肥大细胞的典型特征。本文报道了IL-4诱导人肥大细胞表达FcepsilonR 1，并导致组胺释放的实验结果。我们还发现IL-4促进培养的人肥大细胞的生长以及LFA- 1和ICAM- 1的表达增加，引起细胞的同型聚集。这些结果表明，IL-4是一种强有力的人肥大细胞活化因子，并可能在肥大细胞引起的过敏反应中发挥重要作用。由于过敏性疾病患者的T细胞产生的IL-4的量增加，过敏性个体的肥大细胞可能处于恒定的高反应性状态，并有助于过敏性炎症的所有过程。IL-4对肥大细胞活化的信号转导通路可能在转录水平上受到调控，目前正在研究中。

项目成果

Toru, H: "IL-4 indures homotypic aggregation of human mast cells by promoting LFA-VICAM-i unhesion molecules" Blood. 89. 3296-3302 (1997)

Toru, H：“IL-4 通过促进 LFA-VICAM-i 不聚分子诱导人类肥大细胞同型聚集”血液。

Toru,H., C.Ra S.Nonovama, et al.: "Induction of high affinity IgE receptor(FcεRI) on human mast cells by IL-4" International Immunology. 8. 1367-1373 (1996)

Toru, H., C.Ra S.Nonovama, et al.：“IL-4 对人类肥大细胞的高亲和力 IgE 受体 (FcεRI) 的诱导”，国际免疫学，8. 1367-1373 (1996)。

Toru, H: "Induction of high affinity IgE receptor (FcεRI) on human mast cells by IL-4" Int.Imnunol.8. 1367-1373 (1996)

Toru, H：“IL-4 对人类肥大细胞的高亲和力 IgE 受体 (FcεRI) 的诱导”Int.Imnunol.8 1367-1373 (1996)。

Toru, H.t al.: "IL-4 induces homotypic aggregation of human mast cells by promoting LFA-1/ICAM-1 adhesion molecules." Blood. 89. 3296-3362 (1997)

Toru, H.t al.：“IL-4 通过促进 LFA-1/ICAM-1 粘附分子诱导人类肥大细胞的同型聚集。”

Toru, H.et al.: "Induction of high affinity IgE receptor (FcepsilonRI) on human mast cells by IL-4." Int.Immunol.8. 1367-1373 (1996)

Toru, H.等人：“IL-4 在人类肥大细胞上诱导高亲和力 IgE 受体 (FcepsilonRI)。”