Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice.
Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice.
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DOI：
10.1093/jb/mvj140
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发表时间：
2006-08
影响因子：
2.7
通讯作者：
M. Kanehira;T. Kaifu;K. Maya;Mitsuji Kaji;A. Nakamura;M. Obinata;T. Takai
中科院分区：
文献类型：
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作者：
M. Kanehira;T. Kaifu;K. Maya;Mitsuji Kaji;A. Nakamura;M. Obinata;T. Takai
肥大细胞 (MC) 在针对寄生虫和细菌感染的先天免疫以及超敏反应（例如过敏和自身免疫性疾病的诱导和恶化）中发挥着至关重要的作用。 MC 发育和效应器功能的调节机制对于开发针对此类疾病的新治疗策略具有重要意义。在此，我们报告了从 SV40 大 T 抗原转基因小鼠的温度敏感突变体的骨髓 (BM) 细胞（称为 SVMC）建立了新型永生化 MC 系。 tsSV40LT小鼠的BM细胞在白细胞介素（IL）-3存在下培养3周，然后进行有限稀释和单细胞克隆，产生27个独立的MC克隆，其中三个进行进一步分析。在神经生长因子、干细胞因子和 IL-3 培养中，这些 SVMC 克隆表现出从粘膜 MC 样到结缔组织 MC 样表型的形态和生化变化。这些 SVMC 系表现出显着增强的增殖率，以及对 IgE 介导的细胞内钙动员和脱颗粒的高亲和力 Fc 受体的响应性比来自 BM 的培养 MC 更高。这些细胞系应有助于研究 MC 在健康和疾病中的发育、分化和效应功能的机制。
Mast cells (MCs) play crucial roles in innate immunity to parasitic and bacterial infections as well as in hypersensitivity, such as the induction and exacerbation of allergy and autoimmune diseases. The regulatory mechanisms for MC development and effector functions are of great interest for developing novel therapeutic strategies against such disorders. Here we report the establishment of novel, immortalized MC lines from bone marrow (BM) cells of a temperature-sensitive mutant of SV40 large T antigen-transgenic mice (termed SVMCs). BM cells from tsSV40LT mice were cultured in the presence of interleukin (IL)-3 for 3 weeks, and then subjected to limiting dilution and single-cell cloning, yielding 27 independent MC clones, three of which were subjected to further analysis. On culture with nerve growth factor, stem cell factor and IL-3, these SVMC clones showed morphologic and biochemical changes from mucosal MC-like to connective-tissue MC-like phenotypes. These SVMC lines exhibited a significantly enhanced proliferation rate, and a higher responsiveness to the high affinity Fc receptor for IgE-mediated intracellular calcium mobilization and degranulation than those of BM-derived cultured MCs. These cell lines should facilitate studies on the mechanisms for the development, differentiation and effector functions of MCs in health and diseases.