Actions of thromboxane, prostacyclin, leukotrienes, and lipoxins
THE CONTEXT
Arachidonic acid metabolites regulate vascular reactions, platelet aggregation, and leukocyte recruitment; some also suppress inflammation.
Thromboxane and prostacyclin
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Platelets contain thromboxane synthase and produce thromboxane A2 as their major eicosanoid. Thromboxane A2 promotes platelet aggregation and vasoconstriction.
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Vascular endothelium lacks thromboxane synthase and instead contains prostacyclin synthase.
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Prostacyclin causes vasodilation and strongly inhibits platelet aggregation, helping prevent thrombus formation on normal endothelial cells.
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An imbalance between thromboxane and prostacyclin is implicated as an early event in thrombosis of coronary and cerebral arteries.
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Prostaglandins also contribute to pain and fever.
Leukotriene synthesis and actions
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Leukocytes and mast cells produce leukotrienes through the action of lipoxygenase. These mediators participate in vascular and smooth muscle reactions and leukocyte recruitment.
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Leukotriene synthesis first generates LTA4, which gives rise to LTB4 or LTC4.
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LTB4 is produced by neutrophils and some macrophages and is a potent neutrophil chemoattractant and activator.
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LTC4 and its metabolites LTD4 and LTE4 are produced mainly in mast cells. They cause intense vasoconstriction, bronchospasm, and increased venular permeability. Their bronchospastic action is important in asthma.
Mediators that suppress inflammation
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Lipoxins arise from arachidonic acid through the lipoxygenase pathway. They inhibit neutrophil chemotaxis and adhesion to endothelium, thereby reducing leukocyte recruitment.
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Leukocytes, particularly neutrophils, produce lipoxin intermediates that interacting platelets convert into lipoxins.
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Other antiinflammatory arachidonic acid-derived mediators include resolvins, which resolve the active phase of acute inflammation. Their role remains under study.
Histamine
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Histamine is released from mast cells, basophils, and platelets and causes vasodilation, increased vascular permeability, and endothelial activation.