The Innate Immunity: Roles for New Antifungal and Antibacterial Peptides Secreted by Chromaffin Granules from the Adrenal Medulla

In our search of a function for the chromogranin-derived peptides present within secretory granules of chromaffin cells we observed that a large number of them displayed potent antibacterial and antifungal activities. These peptides are released by exocytosis into the circulation together with catecholamines and are also found in inflammatory fluids together with a variety of other antimicrobial peptides such as defensins. Vasostatin I, the natural N-terminal domain of chromogranin A (1-76), and the vasostatin-derived peptide chromofungin (chromogranin A47-66) are, in addition to fragments of proenkephalin (enkelytin) and ubiquitin (ubifungin), potent antimicrobial peptides of adrenomedullary origin. These peptides interact with the cell wall of fungi and yeast cells and may within minutes penetrate and accumulate within the cells. Once inside, the peptides may target to enzymes that are crucial for the growth of the microorganisms, inhibiting their activities and thus causing the rapid death of the affected species. These properties lead us to propose that these peptides participate in a primary and early line of host defence, acting as a shield against invading microorganisms during stress and infection, linking the neuroendocrine and nervous tissues to the immune system. On the basis of structure, absence of a specific receptor, ability to cross membranes and to inhibit the calmodulin-dependent enzyme calcineurin in vitro, we propose that the vasostatin-derived chromofungin should be recognised as a cell penetrating peptide.