Eicosanoid transcellular biosynthesis : from cell-cell interactions to in vivo tissue responses

The biosynthesis of the biol. active metabolites of arachidonic acid involves a no. of enzymes that are differentially expressed in cells. Prostaglandins and thromboxanes are derived from the chem. unstable prostaglandin (PG) H2 intermediate synthesized by PGH synthases (cyclooxygenase-1/2) and leukotrienes from chem. unstable leukotriene A4 by 5-lipoxygenase. Addnl. enzymes transform these reactive intermediates to a variety of chem. structures known collectively as the lipid mediators. Although some cells have the complete cassette of enzymes required for the prodn. of biol. active prostaglandins and leukotrienes, the actual biosynthetic events often are a result of cell-cell interaction and a transfer of these chem. reactive intermediates, PGH2 and leukotriene A4, between cells. This process has come to be known as transcellular biosynthesis of eicosanoids and requires a donor cell to synthesize and release one component of the biosynthetic cascade and a second, accessory cell to take up that intermediate and process each into the final biol. active product. This review focuses on the evidence for transcellular biosynthetic events for prostaglandins, leukotrienes, and lipoxins occurring during cell-cell interactions. Evidence for arachidonic acid serving as a transcellular biosynthetic intermediate is presented. Expts. for transcellular events taking place in vivo that reveal the true complexity of eicosanoid biosynthesis within tissues are also reviewe