In vitro positive modification of effector functions and subsets of CD64⁺CD32⁺CD16⁺CD11b⁺ and CD64^-CD32⁺CD16⁺CD11b⁺ neutrophil granulocytes from immunocompromised patients with immunosenescence induced by arginyl-α-aspartyl-lysyl-valyl-tyrosyl-arginine

The increasing proportion of elderly and senile individuals in human population causes a problem of age-associated diseases, with immunosenescence playing a key role. Neutrophil granulocytes (NG) are largely susceptible to this process, which requires studying changes in their functioning during immunosenescence and developing methods for experimental correction of NG dysfunctions. Our objective was to clarify the nature of NG dysfunctions during immunosenescence, and to evaluate the effect of synthetic thymic hexapeptide (HP) on the effector functions and CD64⁺CD32⁺CD16⁺CD11b⁺ and CD64^-CD32⁺CD16⁺CD11b⁺ subsets of NG in elderly and senile individuals. The study involved 15 immunocompromised patients aged 60-78 years with chronic obstructive lung disease (COPD), with prolonged and frequent exacerbations (study group 1, SG1), and 30 conditionally healthy volunteers aged 60-74 years (comparison group, CG). We have evaluated the NG subsets (%), i.e., cell subpopulations with CD64, CD32, CD16, CD11b receptors, expression density of these receptors (MFI), phagocytic and microbicidal functions of NG in intact peripheral blood (SG1) and after incubation with tested hexapeptide (10^-6 g/L) for 60 minutes at 37 °C (SG1a). We have revealed an increased contents of CD64⁺CD32⁺CD16⁺CD11b⁺NG subset and a reduced content of the CD64^-CD32⁺CD16⁺CD11b⁺NG subset in SG1 patients in comparison to comparison group, an increased density of CD16 expression along with decreased density of CD11b expression on NG of both subsets. Moreover, an impairment in phagocytic and NADPH-oxidase activity of NG was determined in SG1. Under the influence of the hexapeptide, we have noted a pronounced effect, i.e., a decreased content of CD64⁺CD32⁺CD16⁺CD11b⁺NG and increased number of CD64^-CD32⁺CD16⁺CD11b⁺NG, higher MFI of CD11b on NG of both subsets, digestive functions, stimulated NADPH oxidase activity. The average effect was determined as a decreased MFI of CD16, and an increase in actively phagocyting NG. Low-level effect was registered by the absorption processes, and spontaneous NADPH-oxidase activity of NG. Positive modification of NG functioning under the influence of hexapeptide was shown in vitro upon incubation of NG from immunocompromised patients with immunosenescence.