ProHNPs are the principal α-defensins of human plasma

Abstract

Background: Human neutrophil peptides (HNPs) were discovered as abundant antimicrobial peptides of azurophil granules. Later studies revealed that most HNPs were produced by myelocytes and metamyelocytes and secreted into the bone marrow plasma as the inert proforms, proHNPs. Despite the vast amounts of proHNPs released into bone marrow plasma, little has been done to characterize these. Numerous studies have investigated HNPs in plasma, linking them to a variety of diseases, but without distinguishing between HNPs and their proforms.

Materials and methods: We used an antibody with specificity against the propiece of proHNPs to investigate proHNPs in plasma and tissue.

Results: In contrast to previous studies using HNP antibodies, we found proHNPs to be many-fold more abundant than HNPs in plasma with a mean concentration of 2 μg/mL. The concentration was substantially higher in bone marrow plasma in accordance with the bone marrow being the site of origin of plasma proHNPs. ProHNPs were not bound to high molecular weight plasma proteins. Accordingly, proHNPs were filtered in the kidneys and resorbed in the proximal tubules.

Conclusions: Most HNPs in plasma are in fact proHNPs, which is important given the differences in their origin and biological activities.

Keywords: Alpha-defensins; antimicrobial peptides; myelopoiesis; neutrophils.