Transcellular Metabolism of Leukotrienes in the Lung

  • Timothy D. Bigby
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 314)

Abstract

Leukotrienes are a family of oxygenated metabolites derived from the 5-lipoxygenase pathway of arachidonic acid metabolism via the unstable epoxide intermediate 5(S)5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic acid or leukotriene A4 (LTA4). Leukotrienes have potent effects on inflammatory cell Chemotaxis, adherence, and activation. They also have effects on noninflammatory cells and tissues thus increasing vascular permeability1, inducing smooth muscle contraction, modulating T- and B-cell function2, augmenting natural killer activity3, and inducing fibroblast Chemotaxis4. In humans, the distribution of the 5-lipoxygenase enzyme appears to be limited to inflammatory cells1. Within these cells, the 5-lipoxygenase enzyme is stimulated by millimolar calcium concentrations and ATP 5, associating with the cell membrane via the 5-lipoxygenase-activating protein6. The enzyme then inserts molecular oxygen at the C5 position of unesterified arachidonic acid and, in turn, further converts the resultant hydroperoxide, 5(S)-hydroperoxyeicosatetraenoic acid (5-HPETE), into LTA4. This epoxide is the pivotal intermediate in the 5-lipoxygenase pathway and can be metabolized within inflammatory cells to 5(S),12(R)-dihydroxy-6, 14-cis, 8, 10-trans-eicosatetraenoic acid (leukotriene B4, LTB4) by LTA4 hydrolase or to 5(S)-hydroxy-6(R)-S-glutathionyl-7, 9-trans-ll, 14-cis-eicosatetraenoic acid (leukotriene C4, LTC4) by glutathione-S-transferase 1.

Keywords

Airway Epithelial Cell Epoxide Hydrolase Tracheal Epithelial Cell Human Airway Epithelial Cell Hydroperoxyeicosatetraenoic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Timothy D. Bigby
    • 1
  1. 1.Department of Medicine, San Diego and Veterans Administration Medical CenterUniversity of CaliforniaSan DiegoUSA

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