chapter  30
Pages 56

The leukotrienes (LTs) are generated by de novo synthesis from arachidonic acid when inflammatory cells in the lung are activated. The substances were discovered when the mechanisms for lipoxygenation of arachidonic acid in leukocytes were studied 20 years ago (1). The first compound to be identified was LTB4 (2). Further explorations of this new lipoxygenase pathway resulted in the identification ofLTC4 as a slow reacting substance (SRS) generated in mouse mastocytoma cells activated by the calcium ionophore A23187 (3). It was thereafter established that the biological principle slow reacting substance of anaphylaxis (SRS-A) (4), presumed to be a mediator in asthma and inflammation, indeed was made up of LTC4 and its two closely related metabolites LID4 and L'fE.t (5-12). The leukotriene pathway thus has two main branches, that yielding LTB4 and that resulting in formation of the cysteinylleukotrienes (LTC4, LID4, and L'fE.t) (Fig. 1).