Studies on expression and therapeutsc approach of CD13 in granulomefous lung diseases

细胞表面糖蛋白CD13首先在髓系白细胞中被发现与氨基肽酶N相同（EC 3.4.11.2），由于氨基肽酶的表达被th1相关的细胞因子干扰素-y上调，我们在这里检查了CD13/氨基肽酶N在肺结节病中的意义。结节病患者支气管肺泡灌洗液（BALF）中氨基肽酶活性明显高于正常志愿者（NV）和对照组（CP）。活性与肺结节病活性显著相关。CD13/氨基肽酶N蛋白在结节病患者的肺泡巨噬细胞（AM）中检测到的分子量约为150 Kd，其水平高于NV患者。CD13/氨基肽酶N诱导人淋巴细胞体外趋化迁移，浓度范围为10^<-5> U/ml -10^<-4> U/ml。CD4+ T淋巴细胞的趋化活性高于CD8+ T淋巴细胞。CD13/氨基肽酶N的酶活性降低了趋化活性。结节病患者的BALF中淋巴细胞的趋化活性高于NV患者，而贝司他汀治疗后淋巴细胞的趋化活性明显降低。此外，我们还发现百司他汀可以通过AM抑制结节病患者的促炎细胞因子。本研究提示AM中表达的CD13/氨基肽酶N可能参与了结节病肺T淋巴细胞的浸润和该疾病肺泡炎的发病。

The cell-surface glycoprotein CD13 first identified in leukocytes of the myeloid series is identical to aminopeptidase N (EC 3.4.11.2), Since aminopeptidase expression was shown to be up-regulated by a Th1-related cytokine, interferon-y, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fiuid (BALF) was signaficantly higher in sarcoidosis paitents than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with activity of pulmonary sarcoidosis. CD13/aminopeptodase N proein, which has a molecular mass of approximately 150 Kd, was detectable in alveolar macrophages (AM) from sarcoidosis patients at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentation rage of 10^<-5>-10^<-4> U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from sarcoidosis patients that in that from NV, and the activity was significantly decreased by the treatment with bestatin. Moreover, we found that bestatin can suppress the proinflammatory cytokines by AM from patients with sarcoidosis.This study indicated that CD13/aminopeptidase N expressed in AM may have a role in T lympphocyte involvement in the lung of sarcoidosis and the pahogenesis of alveolitis in this disorder.