Studies on new molecular therapeutic approach for radiation pneumonitis

首先在髓系白细胞中鉴定的细胞表面糖蛋白CD 13与氨肽酶N相同（EC 3.4.11.2）。在这项研究中，我们研究了CD 13/氨基肽酶N在放射性肺纤维化的动物模型中的意义。放射性肺炎大鼠支气管肺泡灌洗液（BALF）中氨肽酶活性在照射后2-4周显著高于对照组。CD 13/氨肽酶N蛋白，其分子量约为150 kD，可检测到肺泡巨噬细胞（AM）从大鼠放射性肺炎在更高的水平比对照组大鼠。放射性肺炎大鼠BALF中淋巴细胞的趋化活性明显高于对照组，经氨肽酶特异性抑制剂bestatin处理后，其趋化活性明显降低，提示AM中表达的CD 13/氨肽酶N可能参与了T淋巴细胞参与放射性肺炎及放射性肺炎肺泡炎的发病过程。我们的研究结果表明，bestatin可能是有用的治疗放射性肺炎。我们正在放射性肺炎的动物模型中测试口服给予bestatin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.