Expression and localization of CYP3A4 and CYP3A5 in human lung
Expression and localization of CYP3A4 and CYP3A5 in human lung
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DOI：
10.1165/ajrcmb.16.3.9070608
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发表时间：
1997-03-01
影响因子：
6.4
通讯作者：
Raunio, H
中科院分区：
文献类型：
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作者：
Anttila, S;Hukkanen, J;Raunio, H
肺中CYP 3A亚家族中原致癌物代谢P450酶的表达可能有助于需要代谢活化的物质（如烟草衍生的多环芳烃）引发肺癌。用免疫组化法测定了人肺中CYP 3A 4和CYP 3A 5蛋白的表达和定位，其中一种抗体特异于CYP 3A亚家族成员，两种抗肽抗体分别特异于CYP 3A 4和CYP 3A 5。在所有具有抗CYP 3A 4和抗CYP 3A 5抗体的患者中观察到肺的一种或多种细胞类型中的阳性免疫染色。抗CYP 3A 4抗体阳性5例，阳性12例。为了确定哪些CYP 3A基因在肺组织中转录，使用CYP 3A 4、CYP 3A 5和CYP 3A 7的基因特异性引物通过逆转录酶-聚合酶链反应进行分析。在研究的所有8份样品中均检测到CYP 3A 5 mRNA，在1份样品中检测到CYP 3A 4 mRNA，在所有样品中均未检测到CYP 3A 7 mRNA。通过免疫组织化学，CYP 3A 5定位于支气管壁的纤毛和粘液细胞、支气管腺体、细支气管柱状和末端立方上皮、I型和II型肺泡上皮、血管和毛细血管内皮以及肺泡巨噬细胞中，而CYP 3A 4发现于支气管腺体、细支气管柱状和末端上皮、II型肺泡上皮以及肺泡巨噬细胞中。这些数据表明，CYP 3A 5是人肺中主要的CYP 3A形式，CYP 3A 4在约20%的个体中表达，并且两种CYP在个体之间的肺表达存在相当大的差异。
Expression in the lung of procarcinogen metabolizing P450 enzymes in the CYP3A subfamily may contribute to the initiation of pulmonary carcinogenesis by agents that require metabolic activation, such as tobacco-derived polycyclic aromatic hydrocarbons. Expression and localization of CYP3A4 and CYP3A5 proteins in human lung were determined by immunohistochemistry with three antibodies, one specific for members of the CYP3A subfamily and two antipeptide antibodies specific for CYP3A4 and CYP3A5, respectively. Positive immunostaining in one or several cell types of the lung was observed in all patients with anti-CYP3A4 and anti-CYP3A5 antibodies. With the anti-CYP3A4 antibody epithelial staining was observed in five cases and staining of alveolar macrophages in 12 of 27 cases. To determine which CYP3A genes are transcribed in lung tissue, analysis by reverse-transcriptase-polymerase chain reaction with gene-specific primers for CYP3A4, CYP3A5, and CYP3A7 was performed. CYP3A5 mRNA was detected in all eight samples studied, CYP3A4 mRNA in one sample, and CYP3A7 mRNA in none of the samples. CYP3A5 was localized by immunohistochemistry in the ciliated and mucous cells of the bronchial wall, bronchial glands, bronchiolar columnar and terminal cuboidal epithelium, type I and type II alveolar epithelium, vascular and capillary endothelium, and alveolar macrophages, whereas CYP3A4 was found in bronchial glands, bronchiolar columnar and terminal epithelium, type II alveolar epithelium, and alveolar macrophages. These data establish that CYP3A5 is the predominant CYP3A form in human lung, that CYP3A4 is expressed in about 20% of individuals, and considerable variation of pulmonary expression occurs in both CYPs between individuals.