Sources, activation, and control of inflammatory mediators
THE CONTEXT
Chemical mediators initiate and regulate inflammation. They may originate from local cells or from circulating precursors activated at the inflammatory site.
Cell-derived mediators
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Cell-derived mediators may be rapidly released from intracellular granules, as with amines, or synthesized anew after stimulation, as with prostaglandins, leukotrienes, and cytokines.
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Tissue macrophages, dendritic cells, and mast cells are the major cellular sources of acute inflammatory mediators.
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Platelets, neutrophils, endothelial cells, and most epithelia also produce some inflammatory mediators.
Plasma-derived mediators
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Plasma-derived mediators, such as complement proteins, are produced mainly in the liver and circulate as inactive precursors.
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These precursors enter inflammatory sites and are activated there, usually through a series of proteolytic cleavages.
Restriction of mediator activity
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Active mediators are produced in response to stimuli such as microbial products and substances released from necrotic cells, restricting inflammation to where and when it is needed.
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Most mediators are short lived: they decay, undergo enzymatic inactivation, or are scavenged or inhibited. These controls prevent excessive reactions.