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Multidrug resistance related molecules in human and murine lung
G L Scheffer1, A C L M Pijnenborg, E F Smit
1Department of Pathology, Free University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Aims:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
The primary lung transporters protecting against pollutants are MDR1 P-glycoprotein (P-gp), MRP1, and major vault protein (MVP). Newer transporters show minimal expression in normal lung tissue, suggesting conserved roles for classic molecules.
Area of Science:
- Pulmonary physiology
- Molecular biology
- Cellular transport mechanisms
Background:
- Multidrug resistance (MDR) proteins like MDR1 P-glycoprotein (P-gp) and MRP1 are implicated in lung protection against inhaled toxins.
- Recent identification of new transporters (e.g., MRP2, MRP3, BCRP) necessitates understanding their role in lung function.
Purpose of the Study:
- To analyze the expression of MDR1, MDR3 P-gp, MRP1, MRP2, MRP3, BCRP, and major vault protein (MVP) in normal human and animal lung tissues.
- To determine the contribution of these transporter proteins to normal lung physiology.
Main Methods:
- Immunohistochemical analysis of frozen normal lung tissue sections from humans and various animal species.
- Utilized a panel of monoclonal antibodies specific for detecting transporter proteins.
Main Results:
- MDR1 P-gp and MRP1 were detected in lung epithelial cell membranes (apical and basolateral, respectively).
- Major vault protein (MVP) showed prominent cytoplasmic staining in lung epithelial cells.
- Newly identified transporters (MRP2, MRP3, BCRP) were undetectable or present at very low levels in lung tissue.
- Strong evolutionary conservation of these transporter proteins was observed across species.
Conclusions:
- MDR1 P-gp, MRP1, and MVP are the key transporters involved in normal lung physiology.
- Further investigation into transporter expression differences between healthy individuals and patients with lung diseases is warranted.