Prostanoids and cell injury.

Abstract

Cells respond to injury with a variety of mechanisms, one of which is the synthesis and release of various vasoactive factors. These factors can influence the intra- and extracellular environments of the cell and thus affect the overall rate of cellular survival. Products of arachidonic acid metabolism represent one such system. Studies have demonstrated the synthesis and release of various prostanoids during global injuries such as circulatory shock, burn injury, myocardial infarction, and severe trauma. We have carried out studies in an isolated, perfused rabbit liver preparation to investigate the cellular stimuli and cellular mechanisms by which the archidonic acid cascade is stimulated under these conditions. Both hypoxia and metabolic poisoning with dinitrophenol are stimuli for enhanced prostanoid production in vitro. This eicosanoid production is associated with evidence of severe cellular injury. In contrast, when endogenous prostanoid production is stimulated in a noninjured liver with phospholipase A2, the production is transient and is not associated with cellular injury. Another stimulus, bacterial endotoxin, has no effect on prostanoid biosynthesis in vitro even though endotoxin is a very potent stimulus in vivo. Activated complement has been shown to be a potent stimulus for arachidonic acid metabolism both in vivo and in vitro. It thus becomes apparent that arachidonic acid metabolism can be influenced by both receptor and nonreceptor related mechanisms in the injured cell. In addition, the eicosanoids released by the injured cell are apparently able to participate in the homeostatic response of the cell to the injury.(ABSTRACT TRUNCATED AT 250 WORDS)