Modulation of Human Complement System by Antimicrobial Peptide Arenicin-1 from Arenicola marina

Abstract

Antimicrobial peptides from marine invertebrates are known not only to act like cytotoxic agents, but they also can display some additional activities in mammalian organisms. In particular, these peptides can modulate the complement system as was described for tachyplesin, a peptide from the horseshoe crab. In this work, we investigated the influence on complement activation of the antimicrobial peptide arenicin-1 from the marine polychaete Arenicola marina. To study effects of arenicin on complement activation in human blood serum, we used hemolytic assays of two types, with antibody sensitized sheep erythrocytes and rabbit erythrocytes. Complement activation was also assessed, by the level of C3a production that was measured by ELISA. We found that the effect of arenicin depends on its concentration. At relatively low concentrations the peptide stimulates complement activation and lysis of target erythrocytes, whereas at higher concentrations arenicin acts as a complement inhibitor. A hypothetical mechanism of peptide action is proposed, suggesting its interaction with two complement proteins, C1q and C3. The results lead to the possibility of the development of new approaches for therapy of diseases connected with complement dysregulation, using peptide regulators derived from natural antimicrobial peptides of invertebrates.

The Interaction of Arenicin-1 With C3b Complement Protein

“…The earlier results of our investigations confirm the literature data about the interactions between C1q and human defensins, tachyplesin-1, arenicin-1 (Ar-1), protegrin-1 form complexes with C1q directly [6]. We also showed that different AMPs possess modulator activity on complement depending on peptide concentrations; in particular, Ar-1 influenced the classical and alternative complement activation pathways [7].…”

Antimicrobial Peptide Arenicin-1 Derivative Ar-1-(C/A) as Complement System Modulator

“…These substances not only participate in host defense against pathogens but they also possess immunomodulatory activity [ 11 ]. In particular, human and non-human AMPs were found to bind complement proteins and to modulate human complement system activity [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Structure, Function, and Therapeutic Potential of Marine Bioactive Peptides

“…Papers included in this Special Issue deal with marine polychaeta, providing good examples of their biological potential. The peptides arenicins and nicomicins, isolated from Arenicola marina [21,22] and Nicomache minor [23], respectively, exhibited in vitro antimicrobial activity and possessed cytotoxicity against cancer cells. Arenicin was shown to modulate the human complement system [22].…”

“…The peptides arenicins and nicomicins, isolated from Arenicola marina [21,22] and Nicomache minor [23], respectively, exhibited in vitro antimicrobial activity and possessed cytotoxicity against cancer cells. Arenicin was shown to modulate the human complement system [22]. At relatively low concentrations, the peptide stimulates complement activation and lysis of target erythrocytes, whereas at higher concentrations arenicin acts as a complement inhibitor [22].…”

“…Arenicin was shown to modulate the human complement system [22]. At relatively low concentrations, the peptide stimulates complement activation and lysis of target erythrocytes, whereas at higher concentrations arenicin acts as a complement inhibitor [22]. The peptide PAP with anticancer activity was purified from the enzymatic hydrolysate of Perinereis aibuhitensis [24].…”