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.
Antimicrobial peptides (AMPs) are not only cytotoxic towards host pathogens or cancer cells but also are able to act as immunomodulators. It was shown that some human and non-human AMPs can interact with complement proteins and thereby modulate complement activity. Thus, AMPs could be considered as the base for complement-targeted therapeutics development. Arenicins from the sea polychaete Arenicola marina, the classical example of peptides with a β-hairpin structure stabilized by a disulfide bond, were shown earlier to be among the most prospective regulators. Here, we investigate the link between arenicins’ structure and their antimicrobial, hemolytic and complement-modulating activities using the derivative Ar-1-(C/A) without a disulfide bond. Despite the absence of this bond, the peptide retains all important functional activities and also appears less hemolytic in comparison with the natural forms. These findings could help to investigate new complement drugs for regulation using arenicin derivatives.
Антимикробные белки и пептиды нейтрофильных гранулоцитов как модуляторы системы комплементаФедеральное государственное бюджетное научное учреждение «Институт экспериментальной медицины» Министерства науки и высшего образования Российской Федерации, 197376, г. Санкт-Петербург, Российская Федерация Резюме Нейтрофильные гранулоциты (нейтрофилы) и система комплемента -важные факторы врожденного иммунитета позвоночных. Вследствие длительной коэволюции между ними сформировались разнообразные отношения. Накоплены данные о действии антимикробных белков и пептидов нейтрофилов на комплемент. В данной работе кратко рассматривается биология нейтрофилов и комплемента, систематизируются работы, посвященные действию миелопероксидазы, активных форм кислорода, лизоцима, антимикробных пептидов, лактоферрина, нейтрофильных внеклеточных ловушек, фрагментов нейтрофилов и тотального вещества гранул на комплемент человека. Акцент делается на физиологической и патофизиологической роли такой модуляции.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.