A study in the mechanism of cell fusion and giant cell fromation in skin diseases

皮肤病细胞融合与巨细胞形成机制研究

• 批准号: 09670875
• 负责人: MIZUTANI Hitoshi
• 金额: $ 1.98万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670875/
• 关键词: cell fusion; syncytium; CD98; monocyte; giant cell; granuloma; membrane fusion; ERP-1

To declare the mechanism of dermal multinuclear giant cells formation, we investigated fusion regulatory protein-1 (FRP-1) expression in the skin lesions of the systemic and cutaneous chronic inflammatory diseases. Immunohistological investigation using anti-FRP-1 monoclonal antibody revealed augmentation of membranous expression of FRP-1 in the inflammatory infiltrates of the early phaselesion of these skin diseases. According to the syncytium formation, the immunoreactive FRP-1 expression was down regulated significantly, and the membrane FRP-1 was no more detective in the matured giant cells. Subsequent, invitro cultured monocytes pulsed with a functional anti-FRP-1 monoclonal antibody induced immunoreactive FRP-1 expression, and its expression was augmented time dependently until the syncytium formation. In contrast, membrane FRP-1expression was downregulated significantly after cell fusion, and it was no more detective in the formed giant cells. These results confirmed involvement of the active FRP-1 membrane protein in the syncytium formation of monocytes and downregulation of membrane FRP-1 is a potent protective mechanism for over-sized giant cell formation.

为了阐明真皮多核巨细胞形成的机制，我们研究了融合调节蛋白-1（FRP-1）在全身性和皮肤慢性炎症性疾病皮损中的表达。免疫组化研究显示，FRP-1的膜表达增强的早期阶段这些皮肤病的炎症浸润。结合胞体的形成，在成熟的巨细胞中，FRP-1的表达明显下调，膜FRP-1的表达消失。随后，体外培养的单核细胞脉冲与功能性抗FRP-1单克隆抗体诱导免疫反应性FRP-1的表达，其表达增强时间依赖性，直到合胞体形成。细胞融合后膜FRP-1表达明显下调，在形成的巨细胞中不再检测到FRP-1表达。这些结果证实了活性FRP-1膜蛋白参与单核细胞的合胞体形成，并且膜FRP-1的下调是过大的巨细胞形成的有效保护机制。

项目成果

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Takahashi,M：“多中心网状组织细胞增多症系统性硬化症和干燥综合征一例”J Dermatol。

Mizutani,H: "Complete remission of recalcitrant polyarteritis nodosa after combination chemotherapy for accompanying B-cell non-Hodgkin lymphoma" Int J Dermatol. 37. 398-389 (1998)

Mizutani,H：“顽固性结节性多动脉炎在伴随 B 细胞非霍奇金淋巴瘤的联合化疗后完全缓解”Int J Dermatol。

Tabata, N.: "Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced cell fusion mediated by HIV gp160" Medical Microbiology & Immunology. 186. 115-123 (1997)

Tabata, N.：“蛋白酪氨酸激酶激活在抗 FRP-1/CD98/4F2 单克隆抗体诱导的 HIV gp160 介导的细胞融合中提供了早期和必需的信号”医学微生物学

Mizutani, H.: "Complete remission of recalcitrant polyarteritis nodosa after combination chemotherapy for accompanying B-cell non-Hodgkin lymphoma." International Journal of Dermatology. 37. 398-399 (1998)

Mizutani, H.：“针对伴随的 B 细胞非霍奇金淋巴瘤的联合化疗后顽固性结节性多动脉炎完全缓解。”