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

CD13在颗粒性肺疾病中的表达及治疗途径研究

基本信息

批准号：
13670602
负责人：
TANI Kenji
金额：
$ 2.3万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670602/
关键词：
granulomafaous diseases lung sarcoidosis CD13 aminopeptidase N bestain T lymplucytes

项目摘要

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.

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）。由于氨肽酶表达被Th 1相关细胞因子干扰素-γ上调，我们在此研究了CD 13/氨肽酶N在肺结节病中的意义。结节病患者支气管肺泡灌洗液（BALF）中氨肽酶活性明显高于正常志愿者（NV）和对照患者（CP）。其活性与肺结节病的活动性显著相关。CD 13/氨肽酶N蛋白分子量约为150 Kd，在结节病患者的肺泡巨噬细胞（AM）中检测到的水平高于NV患者。CD_（13）/氨肽酶N在10 ~ 10 μ U/ml浓度范围内诱导人淋巴细胞的体外趋化迁移<-5><-4>。CD 4 + T淋巴细胞的趋化活性高于CD 8 + T淋巴细胞。CD 13/氨肽酶N的酶活性消除了趋化活性。结节病患者BALF对淋巴细胞的趋化活性高于NV患者，经bestatin治疗后，其趋化活性明显降低。本研究还发现bestatin可抑制结节病患者AM产生的促炎细胞因子，提示AM表达的CD 13/氨基肽酶N可能在结节病肺内T淋巴细胞浸润及肺泡炎的发生中起一定作用。