Examining the role of ABC lipid transporters in pulmonary lipid homeostasis and inflammation

Abstract

Respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are characterised by excessive and persistent inflammation. Current treatments are often inadequate for symptom and disease control, and hence new therapies are warranted. Recent emerging research has implicated dyslipidaemia in pulmonary inflammation. Three ATP-binding cassette (ABC) transporters are found in the mammalian lung - ABCA1, ABCG1 and ABCA3 - that are involved in movement of cholesterol and phospholipids from lung cells. The aim of this review is to corroborate the current evidence for the role of ABC lipid transporters in pulmonary lipid homeostasis and inflammation. Here, we summarise results from murine knockout studies, human diseases associated with ABC transporter mutations, and in vitro studies. Disruption to ABC transporter activity results in lipid accumulation and elevated levels of inflammatory cytokines in lung tissue. Furthermore, these ABC-knockout mice exhibit signs of respiratory distress. ABC lipid transporters appear to have a crucial and protective role in the lung. However, our knowledge of the underlying molecular mechanisms for these benefits requires further attention. Understanding the relationship between cholesterol and inflammation in the lung, and the role that ABC transporters play in this may illuminate new pathways to target for the treatment of inflammatory lung diseases.

Keywords: ABC transporters; ABCA1; ABCA3; ABCG1; Lipids; Pulmonary inflammation; Surfactant.

Fig. 1

ABC transporters expressed in various cell types of the alveolus. Three ABC transporters, namely ABCA1, ABCG1 and ABCA3, are expressed in lung cells present in the alveolus, notably the alveolar epithelial type I and II cells (ATI and ATII respectively) that line the alveoli or air sacs, and alveolar macrophages that are phagocytes of the pulmonary immune system. LB – lamellar bodies, where ABCA3 contributes lipids that eventually are secreted as surfactants (represented via the black arrow)