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RAS BiologyБиоорганическая химия Russian Journal of Bioorganic Chemistry

  • ISSN (Print) 0132-3423
  • ISSN (Online) 1998-2860

Characterization of combined effects of reactive oxygen metabolites, complement system, and antimicrobial peptides In Vitro

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PII
S0132342325010016-1
DOI
10.31857/S0132342325010016
Publication type
Article
Status
Published
Authors
I. A. Krenev
  • Affiliation:
    Institute of Experimental Medicine
    St. Petersburg State University
Volume/ Edition
Volume 51 / Issue number 1
Pages
3-18
Abstract
Phagocytes activation results in the production of reactive oxygen metabolites (ROM) exerting antimicrobial and host-damaging activity. Although the main pool of papers shows their potentiating action on a key humoral nexus of innate immunity, complement system, the data are controversial. Combined action of ROM with antimicrobial peptides of phagocytes also remains poorly characterized. We have investigated the influence of oxidative burst products on complement activation in different in vitro models. Hydrogen peroxide, including that in medium with Fe-EDTA did not affect parameters of complement activity in human blood serum. HOCl in millimolar concentrations stimulated production of C3a and C5a anaphylatoxins in 80% serum, the effect was inhibited by EDTA. We have identified bivalent ions-independent C5 cleavage in the presence of 16 mM HOCl. At the same time, HOCl served as an inhibitor of the alternative complement pathway in the model of surface-associated activation on rabbit erythrocytes in 5% serum. It inhibited production of C3a (IC50 ~ 4 mM) and C5a as well as serum hemolytic activity (IC50 ~ 0.2 mM); the inhibition of C5a generation was less pronounced in the presence of 4–16 mM HOCl. Decrease in anaphylatoxins generation was also observed in the system with zymosan in 5% serum. Under similar conditions but without activating surfaces, moderate HOCl concentrations enhanced C3a and C5a accumulation; EDTA inhibited this effect completely (C3a) or partially (C5a). Finally, in 70% serum, 16 mM HOCl enhanced the anaphylatoxins accumulation but in the presence of zymosan it inhibited this process almost completely. We hypothesize that HOCl can attack the thioester bond in C3 protein to form C3(HOCl) adduct which is capable of fluid-phase convertases formation; however, the attack of C3b can prevent its covalent fixation on membranes and blocks the complement amplification loop. Besides, we have demonstrated the additive character of the combined action of HOCl with antimicrobial peptides (LL-37 cathelicidin and α-defensins) towards Listeria monocytogenes and Escherichia coli. The data obtained precise the picture of the interaction between bactericidal factors of phagocytes and complement as key participants of the immune defense and host damage.
Keywords
активные метаболиты кислорода хлорноватистая кислота комплемент антимикробные пептиды фагоциты нейтрофилы воспаление C3 анафилатоксины
Date of publication
09.11.2025
Year of publication
2025
Number of purchasers
0
Views
42

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