Arachidonic acid metabolism and prostaglandin production
THE CONTEXT
Arachidonic acid supplies lipid mediators that participate in vascular and cellular reactions of acute inflammation.
Precursor release and metabolic pathways
•
Arachidonic acid (AA) is a 20-carbon polyunsaturated fatty acid present in membrane phospholipids.
•
Cellular phospholipases, mainly phospholipase A2, release AA from membrane phospholipids. These enzymes are activated by inflammatory stimuli, including cytokines, complement products, and physical injury.
•
AA-derived mediators are called eicosanoids. Cyclooxygenases generate prostaglandins, whereas lipoxygenases produce leukotrienes and lipoxins.
•
Eicosanoids bind G protein-coupled receptors on many cell types and can mediate virtually every step of inflammation.
Prostaglandin sources and cyclooxygenases
•
Prostaglandins are produced by mast cells, macrophages, endothelial cells, and many other cell types; they participate in vascular and systemic inflammatory reactions.
•
COX-1 responds to inflammatory stimuli and is also constitutively expressed in most tissues. Its homeostatic functions include renal fluid and electrolyte balance and gastrointestinal cytoprotection.
•
COX-2 is induced by inflammatory stimuli and generates prostaglandins during inflammatory reactions; it is low or absent in most healthy tissues.
Names and vascular effects
•
Prostaglandin letters indicate structural features, while the subscript numeral indicates the number of double bonds.
•
Important mediators listed include PGE2, PGD2, PGF2α, PGI2 (prostacyclin), and TxA2 (thromboxane A2). Specific enzymes act on a pathway intermediate to generate each mediator.
•
PGD2 is the major prostaglandin produced by mast cells, whereas PGE2 is more widely distributed.
•
PGD2 and PGE2 cause vasodilation and increase postcapillary venular permeability, promoting exudation and edema.