ATP-binding cassette (ABC) transporters in normal and pathological lung

Abstract

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases.

Figure 1

Expression of ATP-binding cassette proteins in several cell types of human lung. ABC, ATP-binding cassette; BM, basement membrane; BCRP, breast cancer resistance protein; CFTR, cystic fibrosis transmembrane conductance regulator; MRP, multidrug resistance-associated protein; P-gp, P-glycoprotein. *Conflicting results exist in literature.

Figure 2

Immunohistochemical staining of ATP-binding cassette proteins in human lung. A. apical expression of P-gp in bronchial epithelium (COPD patient; frozen section, antibody C219), B. basolateral expression of MRP1 in bronchial epithelium (COPD patient; antibody MRPr1), C. MRP1 expression in bronchoalveolar lavage cells (healthy individual; antibody MRPr1). Lu, lumen. Scale bar = 25 μM.