Identification of CG-1, a natural peptide antibiotic derived from human neutrophil cathepsin G

Abstract

Cathepsin G is a neutral serine protease of the granzyme B family which is found in human PMN, cells known to be important in the defense of the periodontium against periodontal bacteria. We propose that cathepsin G serves as a "pro-antibiotic" containing peptide domains which express selective antibiotic properties. In this study, we used HPLC to separate the low-molecular-weight peptides derived from the ultrafiltrate of a granule extract from unstimulated PMN. One of the peptides exhibited intense bactericidal activity as determined by radial diffusion overlay assay (against Escherichia coli ML-35P), an amino-terminal sequence "RVSSFLPWIR...", and a 3.1-kDa molecular mass determined by electrospray ionization-mass spectrometry. The sequence and mass are consistent with the C-terminus of cathepsin G deduced by cDNA analysis. These findings support the hypothesis that antibiotic peptides derived from cathepsin G occur naturally in human PMN. Since this is the first naturally occurring antibiotic peptide derived from cathepsin G, we designate it "CG-1".