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

• 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

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.

首次在髓系白细胞中鉴定出的细胞表面糖蛋白 CD13 与氨肽酶 N (EC 3.4.11.2) 相同，由于氨肽酶表达被证明受到 Th1 相关细胞因子干扰素 y 的上调，因此我们在此进行了检查CD13/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）中氨肽酶的活性显着高于正常志愿者（NV）和对照患者（CP）。该活性与肺结节病的活性显着相关。 CD13/氨基肽酶 N 蛋白的分子量约为 150 Kd，在结节病患者的肺泡巨噬细胞 (AM) 中可检测到的水平高于 NV 患者的水平。 CD13/氨基肽酶N在10^-5-10^-4U/ml的浓度范围内诱导人淋巴细胞的体外趋化性迁移。 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的酶活性消除了趋化活性。在结节病患者的 BALF 中检测到比 NV 患者的 BALF 具有更高的淋巴细胞趋化活性，并且用贝他汀治疗后该活性显着​​降低。此外，我们发现贝他汀可以抑制结节病患者的 AM 产生的促炎细胞因子。这项研究表明，AM 中表达的 CD13/氨肽酶 N 可能在结节病肺部 T 淋巴细胞受累以及结节病肺泡炎的发病机制中发挥作用。 。

项目成果

Hase,K., Tani,K., Ohmoto,Y., et al.: "Increased CCR4 expression in acive systemic lupus erybematosus."J.Leukoc.Biot. 70. 749-755 (2001)

Hase,K.、Tani,K.、Ohmoto,Y. 等人：“活动性系统性红斑狼疮中 CCR4 表达增加。”J.Leukoc.Biot。

Huang L.: "Role of CD13/aminopeptidase N in rat lymphocytic alveolitis・・・"Radiat Res. 157. 191-198 (2002)

Huang L.：“CD13/氨肽酶 N 在大鼠淋巴细胞性肺泡炎中的作用......”Radiat Res. 157. 191-198 (2002)

Cui P., et al.: "A novel bioactive 31-aminoacid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes"J.Leukoc.Biol.. 70. 306-312 (2001)

Cui P. 等人：“一种新型生物活性 31-氨基酸内皮素-1 是人类中性粒细胞和单核细胞的有效趋化肽”J.Leukoc.Biol.. 70. 306-312 (2001)

Hase K, et al.: "Increased CCR4 expression in active systemic lupus erythematosus"J.Leukoc.Biol.. 70. 749-755 (2001)

Hase K 等：“活动性系统性红斑狼疮中 CCR4 表达增加”J.Leukoc.Biol.. 70. 749-755 (2001)

Huang,L., Ogushi,F., Tani,K., et al.: "Thrombin promotes fibroblast proliferation during the early stages of experimental radiation pneumontis."Radiat Res. 156. 45-52 (2001)

Huang,L.、Ogushi,F.、Tani,K. 等人：“凝血酶在实验性放射性肺炎的早期阶段促进成纤维细胞增殖。”Radiat Res。