Antibacterial and antifungal activities of vasostatin-1, the N-terminal fragment of chromogranin A

Vasostatin-1, the natural N-terminal 1-76 chromogranin A (CGA)-derived frag ment in bovine sequence, has been purified from chromaffin secretory granul es and identified by sequencing and matrix-assisted laser desorption time-o f-flight mass spectrometry. This peptide, which displays antibacterial acti vity against Gram-positive bacteria at micromolar concentrations, is also a ble to kill a large variety of filamentous fungi and yeast cells in the 1-1 0 mu M range. We have found that the C-terminal moiety of vasostatin-1 is e ssential for the antifungal activity, and shorter active peptides have been synthesized. In addition, from the comparison with the activity displayed by related peptides (human recombinant and rat synthetic fragments), we cou ld determine that antibacterial and antifungal activities have different st ructural requirements. To assess for such activities in vivo, CGA and CGA-d erived fragments were identified in secretory material released from human polymorphonuclear neutrophils upon stimulation. Vasostatin-1, which is stor ed in a large variety of cells (endocrine, neuroendocrine, and neurons) and which is liberated from stimulated chromaffin and immune cells upon stress , may represent a new component active in innate immunity.