Lipoxins: eicosanoids carrying intra- and intercellular messages

Abstract

The lipoxins are a recent addition to the family of biologically active products derived from arachidonic acid. Compounds of this series contain a conjugated tetraene structure and can be generated by the actions of the major lipoxygenases of human tissues (5-, 12-, and 15-LO's). Biosynthesis of the lipoxins from cellular sources of unesterified arachidonic acid is triggered by the initial actions of either the 15-LO or 5-LO followed by additional reactions. Recent results indicate that lipoxins are also generated by receptor-mediated events during cell-cell interactions with the transcellular metabolism of key intermediates. Lipoxin A4 and lipoxin B4 each possess a unique spectrum of biological activities unlike those of other eicosanoids in both in vivo and in vitro systems. Lipoxin A4 stimulates changes in the microvasculature and can block some of the proinflammatory effects of leukotrienes (in vivo). Lipoxin A4 and lipoxin B4 both inhibit natural killer cells (in vitro), and lipoxin B4 displays selective actions on hematopoietic cells. The finding that lipoxin A4 activates isolated protein kinase C suggests that it may also serve an intracellular role in its cell of origin before it is released to the extracellular milieu. Thus, cell-cell interactions, along with multiple oxygenations by lipoxygenases, generate compounds that can regulate cellular responses by serving as both intra- and intercellular messages.