Antimicrobial chromogranins and proenkephalin-A-derived peptides: Antibacterial and antifungal activities of chromogranins and proenkephalin-A-derived peptides.

ABSTRACT

The secretory granules from adrenal medullary chromaffin cells contain a complex mixture of low-molecular mass constituents such as catecholamines, ascorbate, nucleotides, calcium, peptides, and several high-molecular mass water-soluble proteins including chromogranins and proenkephalin-A. These proteins are sequestered into secretory granules in which processing yields a large variety of peptides. These fragments are released into the extracellular space upon cell stimulation and are recovered in blood, lymph, cerebrospinal fluid, and synovial fluid. Some of them have biological activity on cells in an autocrine, paracrine, or endocrine fashion. In addition, we have shown that peptides with antimicrobial activity are present with the secretory chromaffin granules and demonstrated that they are released from stimulated chromaffin cells. We have shown that posttranslational modifications modulate the antimicrobial activities. For some peptides, using confocal laser microscopy, we have examined the interaction of the rhodaminated peptides with biological membranes. In addition, we have shown that chromofungin, the antifungal peptide corresponding to chromogranin A(47-66), can bind calmodulin in the presence of calcium and induce inhibition of calcineurin, a calmodulin-dependent enzyme. Because these antibacterial peptides are colocalized with catecholamines, they may be activated during stress, playing a role as a first protective barrier against bacterial infection, and thus act as factors of the innate immunity shortly after infection and before the induction and mobilization of an adaptative immune system.