Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses.
The cysteinyl leukotrienes (cys-LTs) are a family of potent bioactive lipids that act through two structurally divergent G protein-coupled receptors, termed the CysLT(1) and CysLT(2) receptors. The cloning and characterization of these two receptors has not only reconciled findings of previous pharmacologic profiling studies of contractile tissues, but also has uncovered their expression on a wide array of circulating and tissue-dwelling leukocytes. With the development of receptor-selective reagents, as well as mice lacking critical biosynthetic enzymes, transporter proteins, and the CysLT(1) receptor, diverse functions of cys-LTs and their receptors in immune and inflammatory responses have been identified. We review cys-LT biosynthesis; the molecular biology and distribution of the CysLT(1) and CysLT(2) receptors; the functions of cys-LTs and their receptors in the recruitment and activation of effector leukocytes and induction of adaptive immunity; and the development of fibrosis and airway remodeling in animal models of lung injury and allergic inflammation.
Kanaoka
Yoshihide
Y
Department of Medicine, Harvard University Medical School and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston MA 02115, USA.
Boyce
Joshua A
JA
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D018448:Models, Immunological; D009130:Muscle, Smooth / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000503:physiopathology; D018077:Receptors, Leukotriene / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013189:SRS-A / Q000032:analysis / Q000502:physiology*
D016207:Cytokines; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D013189:SRS-A; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor