title: 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.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Chai
authors.affiliation: Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia. Alaina.Ammit@uts.edu.au.|School of Life Sciences, University of Technology, Sydney, NSW, Australia. Alaina.Ammit@uts.edu.au.
authors.forename: Alaina J
authors.initials: AJ
authors.lastname: Ammit
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Ingrid C
authors.initials: IC
authors.lastname: Gelissen
mesh_terms: D000073874:ATP Binding Cassette Transporter, Subfamily A / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D050356:Lipid Metabolism / Q000276:immunology*; D008055:Lipids / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D011014:Pneumonia / Q000276:immunology*
chemical_list: D000073874:ATP Binding Cassette Transporter, Subfamily A; D016207:Cytokines; D008055:Lipids
keywords: ABC transporters; ABCA1; ABCA3; ABCG1; Lipids; Pulmonary inflammation; Surfactant