Influence of Increased sCD56 and Scd16 Serum Concentrations on the Secretory and Cytotoxic Activities of Peripheral Bloodmononuclear Cells in Healthy People Living in Arctic Russia

Abstract

Abstract Objectives. The CD56 differentiation cluster has been found on cells of neurogenic origin, muscle, natural killer cells, and on various populations of T lymphocytes, neutrophils, monocytes, epithelial and dendritic cells; this cluster sends signals to activate the secretion of chemokines, integrins, enzymes, cytokines, and other biologically active substances that are characteristic for this cell type. The CD16 third receptor for Fc immunoglobulins (FcγRIII) has been found on the membranes of granulocytes, mast cells, monocytes, macrophages, natural killers, and lymphocytes. The Fc fragment of antibodies provides the cytophilicity of immunoglobulins and frequently binds to IgM, IgA, and IgE. The aim of this study was to evaluate the effect of elevated concentrations of sCD56 and sCD16 on the secretory and cytotoxic activity of peripheral blood mononuclear cells in healthy people. Methods. An immunological examination was performed on 178 healthy people aged 21 to 55 years, including 112 women and 66 men, living in the Murmansk region and on the Spitsbergen (Svalbard) archipelago. The peripheral venous blood was analyzed; specifically, the hemogram, phagocytic activity of neutrophilic leukocytes, and contents of lymphocyte phenotypes (CD3+, CD4+, CD8+, CD10+, CD16+, CD56+, CD25+, CD71+, HLADRII, CD95+) were determined using an Epics XL instrument (Beckman Coulter, USA). The concentrations of free sCD16, sCD56, cytokines IL-1β, IL-6, TNF-α, IL-10, cGMP and cAMP, and circulating immune complexes (CICs) to IgA, IgM, and IgG were evaluated using an Evolis automatic analyzer (Bio-Rad, Germany). Results. Increases in the serum concentrations of sCD56 and sCD16 in healthy adults of working age are associated with an increase in the content of circulating mononuclear cells with the corresponding membrane clusters. An increase in sCD16 concentration is associated with a decrease in circulating leukocytes in the blood, and an increase in sCD56 concentration is associated with an increase in cytokines. Concentrations of CICs increase in parallel with increases in sCD16 and sCD56 concentrations. An increase in signal-sending activity with an increase in circulating CD16 + and CD56 + leukocytes and the shedding of these signaling molecules occur in parallel with decreases in the cAMP and cGMP concentrations. Conclusion. The increase in serum concentrations of sCD56 and sCD16 reflects the specificity and activity of the functions they perform. Membrane CD56 sends a signal that activates cell secretory activity, which results in increases in serum cytokine and immunoglobulin concentrations. In addition, membrane CD56 initiates cell interaction with immunoglobulins. The interaction of mCD16 and sCD16 with immunoglobulins causes a decrease in circulating lymphocytes in the blood and an increase in serum CIC concentration. The activation of signal transduction through CD56 and CD16 and their shedding occur in parallel with a twofold decrease in the extracellular cAMP and cGMP concentrations.