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Lactoferrin, myeloperoxidase, and ceruloplasmin: complementary gearwheels cranking physiological and pathological processes

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An Erratum to this article was published on 30 July 2014

Abstract

Copper-containing plasma protein ceruloplasmin (Cp) forms a complex with lactoferrin (Lf), an iron-binding protein, and with the heme-containing myeloperoxidase (Mpo). In case of inflammation, Lf and Mpo are secreted from neutrophil granules. Among the plasma proteins, Cp seems to be the preferential partner of Lf and Mpo. After an intraperitoneal injection of Lf to rodents, the “Cp–Lf” complex has been shown to appear in their bloodstream. Cp prevents the interaction of Lf with protoplasts of Micrococcus luteus. Upon immunoprecipitation of Cp, the blood plasma becomes depleted of Lf and in a dose-dependent manner loses the capacity to inhibit the peroxidase activity of Mpo, but not the Mpo-catalyzed oxidation of thiocyanate in the (pseudo)halogenating cycle. Antimicrobial effect against E. coli displayed by a synergistic system that includes Lf and Mpo–H2O2–chloride, but not thiocyanate, as the substrate for Mpo is abrogated when Cp is added. Hence, Cp can be regarded as an anti-inflammatory factor that restrains the halogenating cycle and redirects the synergistic system Mpo–H2O2–chloride/thiocyanate to production of hypothiocyanate, which is relatively harmless for the human organism. Structure and functions of the “2Cp–2Lf–Mpo” complex and binary complexes Cp–Lf and 2Cp–Mpo in inflammation are discussed.

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Abbreviations

Cp:

Ceruloplasmin

Lf:

Lactoferrin

Mpo:

Myeloperoxidase

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Acknowledgments

This study was supported by RFBR grants № 12-04-00301; 13-04-01191, MK-6062.2014.4 and by the Program “Human Proteome”. The authors are grateful to Professor V. N. Kokryakov for generously providing leukocytes of healthy donors, to Dr. M. N. Berlov for kind assistance in mastering the evaluation of antimicrobial activity of proteins, to Dr. M. O. Pulina and Dr. A. N. Skvortsov for CD-spectra measurement.

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Authors and Affiliations

  1. N-W Branch of the Russian Academy of Medical Sciences, Institute for Experimental Medicine, Pavlov Street 12, Saint Petersburg, 197376, Russia

    Alexey V. Sokolov, Elena T. Zakahrova, Valeria A. Kostevich & Vadim B. Vasilyev

  2. Saint-Petersburg State University, Mendeleevskaya Line, Saint Petersburg, 199000, Russia

    Alexey V. Sokolov & Vadim B. Vasilyev

  3. Research Institute of Physico-Chemical Medicine, ul. Malaya Pirogovskaya 1a, Moscow, 119435, Russia

    Alexey V. Sokolov & Valeria A. Kostevich

  4. Institute of Crystallography, RAS, Leninsky pr 59, Moscow, 117333, Russia

    Valeria R. Samygina

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  1. Alexey V. Sokolov
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  2. Elena T. Zakahrova
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  3. Valeria A. Kostevich
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Correspondence to Alexey V. Sokolov.

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Sokolov, A.V., Zakahrova, E.T., Kostevich, V.A. et al. Lactoferrin, myeloperoxidase, and ceruloplasmin: complementary gearwheels cranking physiological and pathological processes. Biometals 27, 815–828 (2014). https://doi.org/10.1007/s10534-014-9755-2

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