Transcellular metabolism of eicosanoids.

In this chapter, current concepts of eicosanoid biochemistry and function have been summarized. Emphasis has been placed on the importance of ascertaining a complete profile of eicosanoids synthesized by a given tissue under varying conditions of stimulation. The concept of transient intermediates, which are involved in each of the known pathways, was reviewed. Such intermediates can also represent substrate for cell-cell interactions, which have been classified and discussed. Knowledge of the synthetic mechanisms, metabolism, and catabolism of eicosanoids has surpassed our comprehension of their biologic actions. It can be speculated that eicosanoids reinforce or synergize normal homeostatic mechanisms that might proceed less effectively in their absence but occur more efficiently when they are produced. Incomplete comprehension of the functional role of eicosanoids has retarded the development of definitive pharmaceutical approaches toward inhibition or stimulation of eicosanoid production in pathophysiologic situations. With regard to thrombosis, the inflammatory response and host-defense mechanisms, leukotrienes, which have been shown to act on vascular endothelium and smooth muscle, may play an important role in occlusive vascular disease. Since leukotrienes and other hydroxy acids such as 12-HETE are not inhibited by aspirin or nonsteroidal anti-inflammatory agents, development of a unifying concept is difficult. It appears that we are approaching a point in time for reevaluation and reassessment of the role of the eicosanoid pathway in hemostasis and thrombosis. Most importantly, recent eicosanoid research has provided answers to biologic phenomena that were not explicable in the past and also explains why therapeutic trials in occlusive vascular disease were not as successful as predicted on theoretical grounds.