Scheffer G L, Pijnenborg A C L M, Smit E F, Müller M, Postma D S, Timens W, van der Valk P, de Vries E G E, Scheper R J
Department of Pathology, Free University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
J Clin Pathol. 2002 May;55(5):332-9. doi: 10.1136/jcp.55.5.332.
Transporter proteins known to mediate multidrug resistance (MDR) in tumour cells--MDR1 P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1)--are thought to be involved in protecting the lungs against inhaled toxic pollutants. Recently, several new transporter family members have been identified--for example, MRP2, MRP3, and breast cancer resistance protein (BCRP). To study the possible contribution of these proteins and the earlier defined MDR1 and MDR3 P-gp molecules, MRP1, and the major vault protein (MVP) to lung functioning, their expression was analysed in normal lung tissue of humans and several animal species.
Frozen sections of normal lung tissues were examined for the expression of the multidrug resistance associated proteins, using an extended panel of monoclonal antibodies that specifically detect these proteins in immunohistochemical techniques.
In line with earlier reports, the expression of MDR1 P-gp and MRP1 was readily detected in the apical and basolateral membranes, respectively, of the epithelial cell layers of the lungs. In addition, prominent cytoplasmic MVP staining was detected in these layers. In contrast, the recently discovered transporters were either undetectable or they were present at very low values in lung tissue. Immunohistochemical staining in tissues from mice, rats, and guinea pigs points to a strong evolutionary conservation for these transporter proteins.
These results show that the "classic" MDR related molecules, MDR1 P-gp, MRP1, and MVP, should be considered the most important transporters in normal lung physiology. It will be of great interest to investigate differences in expression of both classic and newly defined transporters between normal individuals and-for example, patients with various bronchopulmonary pathological conditions.
已知介导肿瘤细胞多药耐药（MDR）的转运蛋白——MDR1 P-糖蛋白（P-gp）和多药耐药相关蛋白1（MRP1）——被认为参与保护肺部免受吸入性有毒污染物的侵害。最近，已鉴定出几个新的转运蛋白家族成员，例如MRP2、MRP3和乳腺癌耐药蛋白（BCRP）。为了研究这些蛋白以及先前定义的MDR1和MDR3 P-gp分子、MRP1和主要穹窿蛋白（MVP）对肺功能的可能作用，分析了它们在人类和几种动物物种的正常肺组织中的表达。
使用一组在免疫组织化学技术中能特异性检测这些蛋白的单克隆抗体，检查正常肺组织的冰冻切片中多药耐药相关蛋白的表达。
与早期报告一致，在肺上皮细胞层的顶端和基底外侧膜中分别很容易检测到MDR1 P-gp和MRP1的表达。此外，在这些层中检测到明显的细胞质MVP染色。相比之下，最近发现的转运蛋白在肺组织中要么检测不到，要么含量极低。对小鼠、大鼠和豚鼠组织的免疫组织化学染色表明，这些转运蛋白具有很强的进化保守性。
这些结果表明，“经典的”MDR相关分子，即MDR1 P-gp、MRP1和MVP，应被视为正常肺生理学中最重要的转运蛋白。研究正常个体与例如患有各种支气管肺部病理状况的患者之间经典转运蛋白和新定义转运蛋白表达的差异将非常有趣。
