Prostaglandins in Mediators of Inflammation
المؤلف:
Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Jon C. Aster, MD, PhD
المصدر:
Robbins & Cotran Pathologic Basis of Disease
الجزء والصفحة:
10th E ,P84-85
2025-11-08
45
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 cyclooxgenases, called COX-1 and COX-2. COX-1 is produced in response to inflammatory stimuli and is also constitutively expressed in most tissues, where it may serve a homeostatic function (e.g., fluid and electrolyte balance in the kidneys, cytoprotection in the gastrointestinal tract). In contrast, COX-2 is induced by inflammatory stimuli and thus generates the prostaglandins that are involved in inflammatory reactions, but it is low or absent in most normal tissues.
Prostaglandins are divided into series based on structural features as coded by a letter (PGD, PGE, PGF, PGG, and PGH) and a subscript numeral (e.g., 1, 2), which indicates the number of double bonds in the compound. The most important ones in inflammation are PGE2, PGD2, PGF2a, PGI2 (prostacyclin), and TxA2 (thromboxane A2), each of which is derived by the action of a specific enzyme on an intermediate in the pathway. Some of these enzymes have restricted tissue distribution. For example, platelets contain the enzyme thromboxane synthase, and hence TxA2 is the major product in these cells. TxA2, a potent platelet-aggregating agent and vasoconstrictor, is itself unstable and rapidly converted to its inactive form TxB2. Vascular endothelium lacks thromboxane synthase but possesses 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 also markedly potentiates the permeability-increasing and chemotactic effects of other mediators. A thromboxane-prostacyclin imbalance has been implicated as an early event in thrombus formation in coronary and cerebral blood vessels. PGD2 is the major prostaglandin made by mast cells; along with PGE2 (which is more widely distributed), it causes vasodilation and increases the permeability of postcapillary venules, thus potentiating edema formation. PGF2a stimulates the contraction of uterine and bronchial smooth muscle and small arterioles, and PGD2 is a chemoattractant for neutrophils.
In addition to their local effects, the prostaglandins are involved in the pathogenesis of pain and fever in inflammation. PGE2 is hyperalgesic and makes the skin hypersensitive to painful stimuli, such as intradermal injection of suboptimal concentrations of histamine and bradykinin. It is involved in cytokine-induced fever during infections.
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