Contradictory effect of recombinant interferon α2b on the non-transformed and transformed phenotypes of functionally significant subpopulations of neutrophilic granulocytes in vitro

Abstract

Introduction. Modern studies demonstrate the multifunctionality of neutrophil granulocytes (NG) and indicate the presence of various NG subpopulations. Each of the NG subpopulations has its own phenotypic and functional features. NG subpopulations reveal plasticity and can change their phenotype under influences of the microenvironment, exerting both positive and negative (suppressing, damaging) effects on the course of the infectious and inflammatory process.

The aim of the study was to determine the possibility of experimental reprogramming of the transformed phenotype of functionally significant NG subpopulations in children with acute small purulent infection (SPI) under the influence of the substance of recombinant interferon α2b (rIFNα2b) in the in vitro system.

Material and methods. Samples of peripheral blood (PB) of 12 children of both sexes aged 2-4 years with acute small purulent infection (MGI) (the study group) and 7 conditionally healthy children, comparable in gender and age (the group of comparison), were studied. The number of NG subpopulations СD64-CD16+CD32+CD11b+, СD64+CD16+CD32+CD11b+, CD62L+СD63-, CD62L+СD63+ was determined by flow cytometry, with refinement of their phenotype by the expression density of each studied membrane molecule according to MFI. Phagocytic and microbicidal functions of NG were studied in children of the both groups. PB samples from children of the study group and the group of comparison were incubated in the in vitro system for 1 h at 370С with a rIFNα2b at a final concentration of 10-6 g/l, after which the features of transformation of the phenotype of NG subpopulations in both groups of children were monitored.

Results. Variants of negative transformation of phenotypes of functionally significant NG subpopulations were found: an increase in the number of activated CD62LdimCD63mid-NG, СD64dimCD16midCD32dimCD11bbright-NG against the background of a decrease in the level of the major subpopulation СD64-CD16midCD32dimCD11bbright and violations of phagocytic and microbicidal functions of NG. A subpopulation of СD64dimCD16midCD32dimCD11bbright-NG with inadequate pro-inflammatory properties was identified. It was shown the possibility of phenotype reprogramming of various NG subpopulations in study group with SPI under the influence of rIFNα2b, which contributed to the positive regulation of the functional cell activity.

Conclusion. Our study demonstrated negative transformation of the phenotype of functionally significant NG subpopulations in children with SPI. The immunomodulatory effects of rIFNα2b were shown on the negatively transformed NG phenotype in study group with the local purulent process. Those effects were manifested in the switch of NG phenotype from the pro-inflammatory to the anti-inflammatory one.

Keywords:neutrophilic granulocytes; subset; phenotype; purulent infection

For citation: Nesterova I.V., Chudilova G.A., Kovaleva S.V., Rusinova T.V., Pavlenko V.N., Tarakanov V.A., Barova N.K., Malinovskaya V.V. Contradictory effect of recombinant interferon α2b on the non-transformed and transformed phenotypes of functionally significant subpopulations of neutrophilic granulocytes in vitro. Immunologiya. 2020; 41 (1): 112–124. DOI: 10.33029/0206-4952-2020-41-2-124-134

Funding. The study was carried out as part of the state assignment of the Ministry of Health of the Russian Federation №AAAA-A18-118122690053-0 and was partially funded by RFBR according to the research project №19-415-230001р_а.

Conflict of interests. The authors declare no conflict of interests.

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