Archives of Toxicology

, Volume 79, Issue 10, pp 600–609 | Cite as

Expression of lung resistance-related protein, LRP, and multidrug resistance-related protein, MRP1, in normal human lung cells in long-term cultures

  • Thomas Lehmann
  • Abdel-Rahman Wageeh Torky
  • Ekkehard Stehfest
  • Stefan Hofmann
  • Heidi Foth
Organ Toxicity and Mechanisms
First Online:
Received:
Accepted:

Abstract

Transport processes form part of the body’s defense mechanism, and they determine the intracellular levels of many endogenous and exogenous compounds. The multidrug resistance-related protein MRP1 and the lung resistance-related protein LRP are associated with drug resistance against chemotherapeutics; they protect cells against toxic compounds. There is much experimental evidence to suggest that both of these transporter proteins serve important physiological functions. The expression of LRP and MRP1 was studied in normal human bronchial epithelial cells (NHBEC) and peripheral lung cells (PLC) obtained from explant cultures from morphologically-normal human lung tissue taken from patients with lung cancer. LRP (mRNA and protein) was detected in the cells of the bronchi as well as the peripheral lung with low (a factor of 2.6) inter-individual variation in the first generation. No significant alterations were noted for LRP within three-to-four generations in the same patient. LRP expression was not substantially different between cultures from different topographic regions of the human lung. MRP1 protein and MRP1 mRNA could also be detected in all of the NHBEC and PLC cultures studied, but with substantially higher (a factor of 7.7) intra-individual variation in the first generation than for LRP. MRP expression was the same for bronchial cells and PLC when the material was obtained from both sites. The level of mRNA for MRP1 was, in general, less stable than that for LRP. In multigeneration explant cultures, the levels of LRP mRNA and protein and MRP1 protein did not fluctuate greatly, but the level of MRP1 mRNA dropped to about 25% of the reference value within four generations (after about 8–10 weeks of culture). In one case, NHBEC subpassages were followed over a period of 20 weeks. In this system MRP mRNA levels increased by more than threefold, while levels of MRP1 protein and LRP mRNA and protein were expressed at almost constant rates.

Keywords

Bronchial Epithelium Normal Human Bronchial Epithelial Cell Major Vault Protein MRP1 Protein Normal Bronchial Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgements

We thank Ursula May, Hedwig Grygier and Dagmar Funk for excellent technical assistance. We thank Dr. KI Hirsch-Ernst for fruitful discussion. The study was supported by a grant from Saxony-Anhalt (2310A/0085G, Morphology of human lung cell cultures) and by a grant from Philip Morris External Research Program (Expression of MRP and LRP in human lung cells).

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Thomas Lehmann
    • 1
    • 2
  • Abdel-Rahman Wageeh Torky
    • 1
  • Ekkehard Stehfest
    • 1
  • Stefan Hofmann
    • 3
  • Heidi Foth
    • 1
  1. 1.Institute of Environmental ToxicologyUniversity of HalleHalleGermany
  2. 2.University of PittsburghPittsburghUSA
  3. 3.Clinic of Cardiothoracic SurgeryUniversity of HalleHalleGermany

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