ABSTRACT
Leukotrienes are oxygenated products of arachidonic acid produced by the action of 5-lipoxygenase via the epoxide intermediate leukotriene A4 (LTA4). The term leukotriene was originally coined because these products were synthesized from arachidonic acid by leukocytes and carried conjugated trienes (1). Since their discovery, leukotrienes have been implicated as key mediators in a wide variety of disorders, including asthma. This chapter reviews the cell biology of the 5lipoxygenase pathway. The first half of this chapter focuses on the spectrum of cells capable of biosynthesis of 5-lipoxygenase-derived products, their relative ability to generate bioactive products, variations among species, the stimuli for biosynthesis, the regulation of expression of the enzymatic machinery necessary for leukotriene formation, and the unique properties of the 5-lipoxygenase pathway in the lung, especially in asthma. The second half of this chapter focuses on leukotriene and lipoxin transcellular biosynthesis, defined as the cooperative formation of products by two or more cell types, the impact of select cytokines and cell adhesion on 5-lipoxygenase-derived eicosanoid formation, the relationship between leukotriene and lipoxin biosynthesis, lipoxin generation in vivo, and transcellular arachidonate metabolism in respiratory tissues. Except where specifically noted, we will focus on eicosanoid biosynthesis in human cell types and tissues because of significant species differences that exist in features of
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the 5-lipoxygenase pathway. These species differences will also be specifically reviewed in the hope that this knowledge may provide insights into eicosanoid biochemistry and biology, as well as insights into human diseases, including asthma.
