Cyclic nucleotides, possible intracellular mediators of macrophage activation and secretory processes.

Macrophages from various sources can be stimulated by a variety of substances to secrete a range of inflammatory mediators and degradative enzymes. The mechanisms involved in the activation and secretory processes are unknown, However, recent evidence suggests that cyclic AMP may play a role in the regulation of neutral protease secretion. Thus, it has been shown that agents known to increase intracellular cyclic AMP levels (cyclic AMP analogues, phosphodiesterase inhibitors, prostaglandin E1 and E2, catecholamines, cholera toxin and, indirectly, glucocorticosteroids) inhibit the secretion of the neutral protease plasminogen activator. It is speculated that macrophage activation may also initiated by changes in the steady-state levels of cyclic nucleotides. A decrease in intracellular cyclic AMP and/or an increase in cyclic GMP levels would favour secretion. It is possible that these changes could be brought about by the action of various stimuli to modify the capacity of the macrophage to synthetize or degrade cyclic nucleotides.