CELL BIOLOGY OF THE 5-LIPOXYGENASE PATHWAY

The initial enzymatic steps in leukotriene synthesis occur at the nucl ear envelope. Cytosolic phospholipase A(2) translocates from the cytop lasm to selectively hydrolyze nuclear envelope phospholipids, releasin g free arachidonate. 5-Lipoxygenase-activating protein, an arachidonat e transfer protein, then binds arachidonate and presents it to 5-lipox ygenase (5-LO), which catalyzes a two-step reaction to produce leukotr iene A(4). In resting human and rat peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat basophilic leukemia cells and h uman alveolar macrophages, however, it is found predominantly in the n ucleus. Immunofluorescence microscopy studies demonstrate that both cy toplasmic and nuclear 5-LO move to the nuclear envelope following cell activation, Many questions remain unanswered regarding the significan ce of nuclear 5-LO, potential autocrine actions of leukotrienes, and i ntracellular trafficking of these enzymes and their products.