Ujike-Asai Azusa, Okada Aki, Du Yuchen, Maruyama Mitsuo, Yuan Xunmei, Ishikawa Fuyuki, Motoo Yoshiharu, Isobe Kenichi, Nakajima Hideo
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Japan.
J Leukoc Biol. 2007 Aug;82(2):429-35. doi: 10.1189/jlb.1006638. Epub 2007 Apr 24.
Telomerase is critically important for the maintenance of a constant telomere length, which in turn, is related to the concepts of longevity and oncogenesis. In addition, it has been well documented that telomerase activity is expressed in immune cells in a highly regulated manner. We have studied systemic anaphylaxis in mouse telomerase reverse transcriptase knockout (mTERT(-/-)) mice to understand the significance of telomerase activity and telomere stability in mast cells, which induce a type I allergic response. Compared with wild-type mice, mTERT(-/-) mice displayed largely attenuated, IgE-mediated, passive anaphylactic responses, which were observed even in the early generations of mTERT(-/-) mice, and had decreased numbers of mast cells in vivo and impaired development of bone marrow-derived mast cells (BMMCs) induced by IL-3 or stem cell factor in vitro. Moreover, in mTERT(-/-) mice, BMMCs exhibited a large morphology and low proliferation rate, while they possessed a comparable degranulation capacity and cell surface expression level of c-kit and FcepsilonRI. These findings imply that telomerase activity has a definitive impact on the type I allergic response by altering the character of effecter mast cells.
端粒酶对于维持恒定的端粒长度至关重要，而端粒长度又与长寿和肿瘤发生的概念相关。此外，已有充分文献记载，端粒酶活性在免疫细胞中以高度调控的方式表达。我们研究了小鼠端粒酶逆转录酶基因敲除（mTERT(-/-)）小鼠的全身性过敏反应，以了解端粒酶活性和端粒稳定性在诱导I型过敏反应的肥大细胞中的意义。与野生型小鼠相比，mTERT(-/-)小鼠表现出明显减弱的IgE介导的被动过敏反应，即使在mTERT(-/-)小鼠的早期世代也能观察到，并且其体内肥大细胞数量减少，体外由IL-3或干细胞因子诱导的骨髓来源肥大细胞（BMMCs）发育受损。此外，在mTERT(-/-)小鼠中，BMMCs呈现出较大的形态和较低的增殖率，而它们具有相当的脱颗粒能力以及c-kit和FcepsilonRI的细胞表面表达水平。这些发现表明，端粒酶活性通过改变效应肥大细胞的特性对I型过敏反应具有决定性影响。
