Leukotrienes and Lipoxins: Structures, Biosynthesis, and Biological Effects

Arachidonic acid is released from membrane phospholipids upon cell stimulation (for example, by immune complexes and calcium ionophores) and converted to leukotrienes by a 5-lipoxygenase that also has leukotriene A 4 synthetase activity. Leukotriene A 4 , an unstable epoxide, is hydrolyzed to leukotriene B 4 or conjugated with glutathione to yield leukotriene C 4 and its metabolites, leukotriene D 4 and leukotriene E 4 . The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C 4 in luteinizing hormone secretion. Lipoxins are formed by the action of 5- and 15-lipoxygenases on arachidonic acid. Lipoxin A causes contraction of guinea pig lung strips and dilation of the microvasculature. Both lipoxin A and B inhibit natural killer cell cytotoxicity. Thus, the multiple interaction of lipoxygenases generates compounds that can regulate specific cellular responses of importance in inflammation and immunity.