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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Respiratory Research 1/2018

Expression of MATE1, P-gp, OCTN1 and OCTN2, in epithelial and immune cells in the lung of COPD and healthy individuals

Zeitschrift:
Respiratory Research > Ausgabe 1/2018
Autoren:
Tove Berg, Tove Hegelund-Myrbäck, Johan Öckinger, Xiao-Hong Zhou, Marie Brännström, Michael Hagemann-Jensen, Viktoria Werkström, Janeric Seidegård, Johan Grunewald, Magnus Nord, Lena Gustavsson
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12931-018-0760-9) contains supplementary material, which is available to authorized users.

Abstract

Background

Several inhaled drugs are dependent on organic cation transporters to cross cell membranes. To further evaluate their potential to impact on inhaled drug disposition, the localization of MATE1, P-gp, OCTN1 and OCTN2 were investigated in human lung.

Methods

Transporter proteins were analysed by immunohistochemistry in lung tissue from healthy subjects and COPD patients. Transporter mRNA was analysed by qPCR in lung tissue and in bronchoalveolar lavage (BAL) cells from smokers and non-smokers.

Results

We demonstrate for the first time MATE1 protein expression in the lung with localization to the apical side of bronchial and bronchiolar epithelial cells. Interestingly, MATE1 was strongly expressed in alveolar macrophages as demonstrated both in lung tissue and in BAL cells, and in inflammatory cells including CD3 positive T cells. P-gp, OCTN1 and OCTN2 were also expressed in the alveolar epithelial cells and in inflammatory cells including alveolar macrophages. In BAL cells from smokers, MATE1 and P-gp mRNA expression was significantly lower compared to cells from non-smokers whereas no difference was observed between COPD patients and healthy subjects. THP-1 cells were evaluated as a model for alveolar macrophages but did not reflect the transporter expression observed in BAL cells.

Conclusions

We conclude that MATE1, P-gp, OCTN1 and OCTN2 are expressed in pulmonary lung epithelium, in alveolar macrophages and in other inflammatory cells. This is important to consider in the development of drugs treating pulmonary disease as the transporters may impact drug disposition in the lung and consequently affect pharmacological efficacy and toxicity.
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