HB‐107, a nonbacteriostatic fragment of the antimicrobial peptide cecropin B, accelerates murine wound repair

Abstract

Antimicrobial peptides are essential to innate host defense as effectors of pathogen clearance and can modify host cell behaviors to promote wound repair. While these two functions appear interrelated, it is unclear whether the ability to aid in wound repair requires inherent antimicrobial function. We hypothesized that the influence of antimicrobial peptides on wound repair is not dependent on antimicrobial function. To explore this, we analyzed the microbial killing activity of peptide fragments and correlated this with the ability to influence wound repair in mice. HB-107, a peptide lacking antimicrobial activity and originally derived from the antimicrobial cecropin B, showed up to 64 percent improvement in wound repair compared to scrambled peptide and vehicle controls, an effect comparable to treatment with recombinant human platelet-derived growth factor-BB (formulated as Regranex). Wounds treated with HB-107 showed keratinocyte hyperplasia and increased leukocyte infiltration. Furthermore, HB-107 stimulated interleukin-8 secretion from cultured endothelial cells, an effect that may explain the increase in leukocyte migration. These findings confirm that antimicrobial peptides can function as effectors of cutaneous wound repair. Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function.

N-Glycolylneuraminic Acid Deficiency in Mice: Implications for Human Biology and Evolution

“…Murine cutaneous wound repair was evaluated as described previously (22). Sex-and age-matched adult mice were anesthetized by isoflurane inhalation and shaved, and hair was removed by chemical depilation (Nair).…”

Peptide Antimicrobial Agents

“…As previously mentioned, many mammalian antimicrobial or host defense peptides aid in the clearance of invading pathogens not by direct killing but by stimulating the host's innate immune system. Currently, several peptides that display no direct microbicidal activity in vitro are being developed for their ability to either protect against bacterial infection or promote wound healing (24,145).…”

Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections

“…Overall, experimental systems simulating physiologically relevant conditions [9], as well as in vivo animal model infection studies [26], have convincingly demonstrated that cationic host defence peptides are able to limit or clear infections. In addition to exhibiting protective capabilities against a diverse range of pathogens from bacteria, fungi, parasites and viruses [26][27][28][29][30][31][32][33], and protecting against systemic inflammatory syndrome (discussed below), these peptides are also thought to be beneficial in other scenarios such as wound healing [34] and counteracting tumours [35,36]. The potential for beneficial applications of cationic host defence peptides has continued to grow with increased interest in elucidating the mechanisms associated with the protective functions of these defence peptides.…”