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Polyreactive Transformation of Class G Immunoglobulins as a Vector for Search of Potential Means for Improving the Activity of Anti-endotoxin Immunity

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Abstract

Short-term in vitro exposure of a chaotropic reagent to native class G immunoglobulins can significantly increase the activity of anti-endotoxin immunity and cause a decrease in the ability of effector cells for enterobacteria lipopolysaccharides (LPS). This leads to reducing the LPS-dependent activation of these cells and subsequent inflammation. This can be useful not only for the treatment of septic patients, but also for the prevention of the progression of diseases of atherosclerotic nature, because LPS is considered to be the most important factor in the induction of atherogenesis. The polyreactive transformation mechanism of native class G immunoglobulins under the influence of a chaotropic reagent remains unknown. It can consist in the induction of intramolecular conformational rearrangements of native γ-globulins. As a result, “ancestral” sites of low-affinity multispecific binding appear on Fab fragments, which determines the appearance of complementarity to evolutionarily stable molecular structures of pathogens. The results indicate the need for further investigation of the polyreactive transformation mechanisms of native class G immunoglobulins and the search for nontoxic chaotropic agents that could potentially be used in clinical practice.

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ACKNOWLEDGMENTS

The authors are grateful to the staff of the Central Research Laboratory of the Crimean Federal University named after Far Eastern Branch, Russian Academy of Sciences, Vernadsky (Simferopol).

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This work was financially supported by third parties.

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Authors and Affiliations

  1. Vernadsky Crimean Federal University, Georgievsky Medical Academy, 295051, Simferopol, Russia

    A. I. Gordienko, N. V. Khimich, V. A. Beloglazov & A. V. Kubyshkin

  2. Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia

    M. Yu. Yakovlev

  3. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    M. Yu. Yakovlev

Authors
  1. A. I. Gordienko
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  2. N. V. Khimich
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  3. V. A. Beloglazov
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  4. A. V. Kubyshkin
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  5. M. Yu. Yakovlev
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Correspondence to M. Yu. Yakovlev.

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Conflict of interests. The authors declare no apparent and potential conflicts of interest related to the publication of this article.

Statement of compliance with standards of research involving humans as subjects. All studies were conducted in accordance with the principles of biomedical ethics formulated in the Helsinki Declaration of 1964 and its subsequent amendments, and approved by the local bioethical committee of the Crimean Federal University named after Far Eastern Branch, Russian Academy of Sciences, Vernadsky (Simferopol). Each study participant submitted voluntary written informed consent, signed by him after explaining to him the potential risks and benefits, as well as the nature of the forthcoming study.

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Gordienko, A.I., Khimich, N.V., Beloglazov, V.A. et al. Polyreactive Transformation of Class G Immunoglobulins as a Vector for Search of Potential Means for Improving the Activity of Anti-endotoxin Immunity. Hum Physiol 46, 554–559 (2020). https://doi.org/10.1134/S0362119720040052

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  • DOI: https://doi.org/10.1134/S0362119720040052

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