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

Ekaterina S Umnyakova,Alexander V Zhakhov,Vladimir N Kokryakov,Nikolay P Gorbunov,Tatiana V Ovchinnikova,Ilia A Krenev,Mikhail N Berlov

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.

Highlights

The biologically active compounds derived from marine organisms are known to be unique, and can be used as a pattern for the development of new, effective pharmacological agents for treatment of different diseases [1]
We found that the effect of arenicin on the complement system depends on the concentration of the peptide
In the hemolytic assay with antibody sensitized sheep erythrocytes (Esh ), which is the model for the classical pathway of complement activation, we observed more than twice the baseline level of Esh lysis by 1% normal human serum (NHS) in the presence of arenicin-1 at concentrations

Summary

Introduction

The biologically active compounds derived from marine organisms are known to be unique, and can be used as a pattern for the development of new, effective pharmacological agents for treatment of different diseases [1]. Antimicrobial peptides named arenicins are found in coelomocytes of the marine polychaete Arenicola marina. These cationic peptides consist of 21 amino acid residues, and have the structure of a β-hairpin [4,5] stabilized by one (for arenicins-1 and -2) or two (for arenicin-3) intramolecular disulfide bonds. Arenicins have been detected in epithelia of the body wall and gut of A. marina [6]. At micromolar concentrations, these peptides demonstrate significant antimicrobial activity towards a wide range of Gram-positive and Gram-negative bacteria, as well as of fungi [2,3,7,8,9], and they seem to play a significant role in host defense of this polychaete.

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Results

Conclusion