Leukotrienes and Prostacyclin

Volume 54 of the series NATO Advanced Science Institutes Series pp 15-41

The Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation

  • Bengt SamuelssonAffiliated withDepartment of Physiological, Chemistry Karolinska Institutet

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The leukotrienes (LT), originally discovered in leukocytes, are formed from polyunsaturated fatty acids as arachidonic acid. The unstable intermediate LTA4 (5(S)-oxido-trans-7,9-trans,11,14-cis-eicosatetraenoic acid), is converted enzymatically by hydrolysis Tinto LTB4 (5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid), and by addition of glutathione into LTC4 (5(S)-hydroxy,6(R)-S-glutathionyl-7,9-trans,11,14-cis-eicosatetraenoic acid). LTC4 is metabolized to corresponding cystéinylglycine derivative (LTD4) and cysteine derivative (LTE4). Corresponding leukotrienes can be formed from 5,8,11-cis-eicosatrienoic acid and 5,8,11,14,17-cis-eicosapentaenoic acid. LTC4 LTD4 and LTE4 which are identical with slow reacting substance of anaphylaxis, are bronchoconstrictors and increase the permeability of microvasculature. LTB4 is a potent chemotactic agent and increases adhesion of leukocytes to endothelium in postcapillary venules. The leukotrienes might therefore function as mediators both in immediate hypersensitivity reactions and in inflammation.