Studies on new molecular therapeutic approach for radiation pneumonitis

细胞表面糖蛋白CD13首先在髓系白细胞中发现，与氨基肽酶N相同（EC 3.4.11.2）。在这项研究中，我们通过动物模型检测了CD13/氨基肽酶N在辐射诱导肺纤维化中的意义。辐照后2 ~ 4周，放射性肺炎大鼠支气管肺泡灌洗液（BALF）中氨基肽酶活性明显高于对照组。CD13/氨基肽酶N蛋白分子量约为150kd，在放射性肺炎大鼠肺泡巨噬细胞（AM）中检测到的CD13/氨基肽酶N蛋白水平高于对照组大鼠。放射性肺炎大鼠BALF中淋巴细胞的趋化活性高于对照大鼠，且经特异性氨基肽酶抑制剂贝斯特汀治疗后其活性明显降低，提示AM中CD13/氨基肽酶N表达可能参与了T淋巴细胞参与放射性肺炎和肺泡炎的发病过程。我们的研究结果表明，贝司他汀可能对放射性肺炎的治疗有用。我们目前正在放射性肺炎动物模型中测试口服贝司他汀的效果。

The cell-surface glycoprotein CD13 first identified in leukocytes of the myeloid series is identical to aminopeptidase N (EC 3.4.11.2). In this study, we examined here the significance of CD13/aminopeptidase N in radiation-induced pulmonary fibrosis using an animal model. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in rats with radiation pneumonitis at 2-4 weeks after the irradiation than in control rats. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from rats with radiation pneumonitis at higher levels than in those from control rats. Higher chemotactic activity for lymphocytes was detected in the BALF from rats with radiation pneumonitis than that from control rats, and the activity was significantly decreased by the treatment with bestatin, a specific aminopeptidase inhibitor, indicating that CD13/aminopeptidase N expressed in AM may have a role in T lymphocyte involvement in radiation pneumonitisn and the pathogenesis of alveolitis in this disorder. Our results suggest that bestatin may be useful for the treatment of radiation pneumonitis. We are now testing the effect of oral administration of bestatin in animal model of radiation pneumonitis.