Lipid metabolites as regulators of airway smooth muscle function.
Compelling evidence identifies airway smooth muscle (ASM) not only as a target but also a cellular source for a diverse range of mediators underlying the processes of airway narrowing and airway hyperresponsiveness in diseases such as asthma. These include the growing family of plasma membrane phospholipid-derived polyunsaturated fatty acids broadly characterised by the prostaglandins, leukotrienes, lipoxins, isoprostanes and lysophospholipids. In this review, we describe the enzymatic and non-enzymatic biosynthetic pathways of these lipid mediators and how these are influenced by drug treatment, oxidative stress and airways disease. Additionally, we outline their cognate receptors, many of which are expressed by ASM. We describe potential deleterious and protective roles for these lipid mediators in airway inflammatory and remodelling processes by describing their effects on diverse functions of ASM in asthma that have the potential to contribute to asthma pathogenesis and symptoms. These functions include contractile tone development, cytokine and extracellular matrix production, and cellular proliferation and migration.
Clarke
Deborah L
DL
Respiratory Pharmacology, National Heart and Lung Institute, Imperial College, London, UK.
Dakshinamurti
Shyamala
S
Larsson
Anna-Karin
AK
Ward
Jane E
JE
Yamasaki
Akira
A
D000818:Animals; D001980:Bronchi / Q000502:physiology*; D015777:Eicosanoids / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis / Q000502:physiology*; D008956:Models, Chemical; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D012137:Respiratory System / Q000378:metabolism*
D015777:Eicosanoids; D008246:Lysophospholipids