Results presented here support the hypothesis that NE and PR3, proteases that co-localize with myeloid a-defensins, participate in the intracellular maturation of HNP1. In previous studies with HL-60 and chronic myelogenous leukemia cells, Valore and Ganz demonstrated sequential proteolytic processing of proHNP with the formation of a 56-residue intermediate that is subsequently processed to mature HNP. While proHNPs were found exclusively in the cytoplasmic/microsomal fraction, the granule fraction contained only the intermediate and mature HNP [35] . Therefore it is likely that proHNP-processing by NE and PR3 occurs during the packaging of HNPs in azurophil granules. CG processing of proHNP1A produced a peptide that was extended at the amino terminus by two residues (Asn-Met) expressed at the carboxyl terminus of the HNP1 prosegment. Harwig et al. identified a minor form of HNP3 in fully differentiated neutrophils with the same Asn-Met dipeptide extension [41] reported here. Thus, CG processing of proHNP1 may also occur in vivo.