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

Mar Drugs. 2018 Dec 1;16(12):480. doi: 10.3390/md16120480.

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.

Keywords: Arenicola marina; C3a; antimicrobial peptides; arenicin; complement.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / isolation & purification
  • Antimicrobial Cationic Peptides / pharmacology*
  • Complement Activation / drug effects*
  • Complement C1q / agonists
  • Complement C1q / antagonists & inhibitors
  • Complement C1q / immunology
  • Complement C1q / metabolism
  • Complement C3 / agonists
  • Complement C3 / antagonists & inhibitors
  • Complement C3 / immunology
  • Complement C3 / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / drug effects
  • Erythrocytes / immunology
  • Erythrocytes / metabolism
  • Helminth Proteins / isolation & purification
  • Helminth Proteins / pharmacology*
  • Hemolysis / drug effects
  • Humans
  • Polychaeta*
  • Protein Binding / drug effects*
  • Rabbits
  • Sheep

Substances

  • Antimicrobial Cationic Peptides
  • C3 protein, human
  • Complement C3
  • Helminth Proteins
  • arenicin-1, Arenicola marina
  • Complement C1q