Prostaglandins (PGs) are produced by mast cells, macrophages, endothelial cells, and many other cell types, and are involved in the vascular and systemic reactions of inflammation. They are generated by the actions of two cyclooxygenases called COX-1 and COX-2. COX-1 is produced in response to inflammatory stimuli and also is constitutively expressed in most tissues, where it may serve a homeostatic function (e.g., fluid and electrolyte balance in http://ebooksmedicine.net inhibitors, aspirin, indomethacin Lipoxygenase inhibitors the kidneys, cytoprotection in the gastrointestinal tract). In Prostaglandins are named based on structural features contrast, COX-2 is induced by inflammatory stimuli and coded by a letter (e.g., PGD, PGE, PGF, PGG, and PGH) thus generates the PGs that are involved in inflammatory and a subscript numeral (e.g., 1, 2), which indicates the reactions, but it is low or absent in most normal tissues. number of double bonds in the compound. The most important prostaglandins in inflammation are PGE2, PGD2, PGF2a, PGI2 (prostacyclin), and TXA2 (thromboxane A2), Table 3.6 Principal Actions of Arachidonic Acid Metabolites in each of which is derived by the action of a specific enzyme Inflammation on an intermediate in the pathway. Some of these enzymes Action Eicosanoid have restricted tissue distribution and functions.
• PGD2 is the major prostaglandin made by mast cells;
Vasodilation Prostaglandins PGI2 (prostacyclin), PGE1, PGE2, PGD2 along with PGE2 (which is more widely distributed), it causes vasodilation and increases the permeability of
Vasoconstriction Thromboxane A2, leukotrienes C4, D4, E4 postcapillary venules, thus potentiating exudation and resultant edema. PGD2 also is a chemoattractant for
Increased vascular permeability Leukotrienes C4, D4, E4 neutrophils.
Chemotaxis, leukocyte adhesion Leukotriene B4 • Platelets contain the enzyme thromboxane synthase,
Smooth muscle contraction Prostaglandins PGC4, PGD4, PGE4 which is responsible for synthesizing TXA2, the major platelet eicosanoid. TXA2 is a potent platelet-aggregating agent and vasoconstrictor, and thus promotes thrombosis.
In contrast, vascular endothelium contains prostacyclin synthase, which is responsible for the formation of prostacyclin (PGI2) and its stable end product PGF1a. Prostacyclin is a vasodilator and a potent inhibitor of platelet aggregation, and thus serves to prevent thrombus formation on normal endothelial cells. A thromboxane– prostacyclin imbalance has been implicated in coronary and cerebral artery thrombosis (Chapter 4).
In addition to their local effects, prostaglandins are involved in the pathogenesis of pain and fever, two common systemic manifestations of inflammation. PGE2 makes the skin hypersensitive to painful stimuli, and causes fever during infections (described later).