Other inflammatory mediators: PAF, coagulation receptors, kinins, and neuropeptides
THE CONTEXT
Several additional mediator systems influence vascular responses, platelet activation, pain, and inflammatory signaling, although some of their roles remain uncertain.
Platelet-activating factor
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Platelet-activating factor (PAF)* is a phospholipid-derived mediator that causes platelet aggregation.
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PAF can be produced by platelets, basophils, mast cells, neutrophils, macrophages, and endothelial cells.
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PAF causes vasoconstriction and bronchoconstriction; at low concentrations, it induces vasodilation and increased venular permeability.
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Its role in acute inflammatory reactions remains unclear.
Coagulation and inflammation
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Protease-activated receptors (PARs) are activated by thrombin and* are expressed on platelets and leukocytes. Their major role is likely platelet activation during clotting.
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Virtually all tissue injuries that cause clotting also induce inflammation. Inflammation alters endothelial cells in ways that increase the likelihood of abnormal clotting, or thrombosis.
Kinins are vasoactive peptides formed from plasma proteins called kininogens by proteases called kallikreins. Kallikrein cleaves high-molecular-weight kininogen to produce bradykinin.
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Bradykinin increases vascular permeability, contracts smooth muscle, dilates blood vessels, and causes pain when injected into the skin; these effects resemble those of histamine.
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Bradykinin acts briefly because kininase rapidly inactivates it. It has been implicated in some allergic reactions, including anaphylaxis.
Neuropeptides
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Sensory nerves and various leukocytes secrete neuropeptides, which may help initiate and regulate inflammatory responses.
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Examples include substance P and neurokinin A, which are produced in the central and peripheral nervous system.