Production of the growth factors GM-CSF, G-CSF, and VEGF by human peripheral blood cells induced with metal complexes of human serum γ -globulin formed with copper or zinc ions.

Sergey B Cheknev,Alla A Babajanz,Irina E Efremova,Anna S Mezdrokhina,Nadezhda A Moryakova,Maria A Apresova,Lidya S Piskovskaya

doi:10.1155/2014/518265

Sergey B Cheknev, Alla A Babajanz + Show 5 more

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https://doi.org/10.1155/2014/518265

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Abstract

As it was established in our previous studies, the proteins of human serum γ-globulin fraction could interact with copper or zinc ions distributed in the periglobular space, form metal complexes, and become able to perform effector functions differing due to the conformational shifts from those mediated by them in native conformation of their Fc regions. In the present work we have evaluated ability of the γ-globulin metal complexes formed with copper or zinc ions in the conditions like to the physiological ones to induce production or to regulate induction in the culture of freshly isolated human peripheral blood cells (PBC) of granulocyte (G) and granulocyte-macrophage (GM) colony-stimulating factors (CSF) as well as of vascular endothelial growth factor (VEGF). The γ-globulin metal complexes formed with both copper and zinc ions were found to similarly reduce production of GM-CSF, G-CSF, and VEGF induced in normal human PBC cultures by the control γ-globulins or by copper and zinc ions used alone. In context of theory and practice of inflammation the properties of the γ-globulin metal complexes might impact the basic knowledge in search of novel approaches to anti-inflammatory drugs development.

Highlights

The data obtained indicate that GMCSF did appear in the culture medium of normal human peripheral blood cells (PBC) induced with γ-globulin metal complexes, as well as with their control proteins or metal ions used alone not earlier than after 48 hrs of the cells incubation
The present study demonstrates that human serum γglobulins exerted induction of the production by normal human PBC of GM-colony-stimulating factors (CSF) (Figure 1), G-CSF (Figure 2), and vascular endothelial growth factor (VEGF) (Figure 3)
Taking into account that induction of such key cytokines of inflammatory process as IFN-γ, IL-2, IL-1β, IL-6, tumor necrosis factor α (TNF-α), and inhibitory IL-10, due to the properties of γ-globulin metal complexes, might be supported at the balanced state, coincidence in reduced production of GM-CSF, G-CSF, and VEGF by normal human PBC could reflect dynamic shift in the cell activity illustrating achievement by PBC of their functional state beginning which generation of inflammatory inducing signals provided by the growth factors would be reduced

Summary

Introduction

Between cytokines that play key roles in initiation and development of inflammation interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-2, IL-6, IL-12, and tumor necrosis factor α (TNF-α) are produced by activated T cells or macrophages and monocytes (MC), by dendritic cells (DC) and other cell types beginning from the first steps of inflammation till the termination phase of the process [1,2,3,4,5] They act as factors of DC1/DC2, MC1/MC2, and (or) Th1/Th2 polarization of the inflammatory response and form inflammatory environment for cells functioning at the tissue lesions [1, 2, 6,7,8]. They recruit neutrophils, lymphocytes, or MC into the inflammatory lesions, where the cells introduce in regulatory network supporting productive phase of inflammatory response [13, 19,20,21]

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