РЕМОДЕЛЛИНГ ФЕНОТИПА СУБПОПУЛЯЦИЙ НЕЙТРОФИЛЬНЫХ ГРАНУЛОЦИТОВ CD64-CD32+CD16+CD11B+НГ, CD64+CD32+CD16+CD11B+НГ В ЭКСПЕРИМЕНТАЛЬНОЙ МОДЕЛИ ВИРУСНО-БАКТЕРИАЛЬНОЙ ИНФЕКЦИИ В СИСТЕМЕ IN VITRO

The search for new targeted therapeutic strategies based on the study of the immunopathogenetic mechanisms of the occurrence of co-infections is relevant and can further contribute not only to the optimization of the choice of immunotropic drugs, but also to the achievement of positive clinical and immunological remission of atypically occurring infectious processes. Previously, our studies found that recurrent viral-bacterial respiratory infections are associated with dysfunctions of neutrophilic granulocytes (NG) with varying degrees of severity of violations of their effector properties. NG dysfunctions are often associated with various phenotypic profiles characterized by different expression density levels of functionally significant trigger receptors. The aim of the study was to evaluate the transformation of the phenotype of the subsets CD64 - CD32 + CD16 + CD11b + , СD64 + CD32 + CD16 + CD11b +  neutrophilic granulocytes in experimental model of viral-bacterial infection in vitro. We examined 52 blood samples from 13 healthy adult volunteers. Samples were incubated with formyl-methionyl-leucyl-phenylalanine (fMLP), double-stranded RNA (dsRNA) and under conditions of co-incubation. The phenotypic characteristics of the subsets of CD64 - CD32 + CD16 + CD11b + NG, СD64 + CD32 + CD16 + CD11b + NG were determined using MAbs CD16-ECD, CD64-FITC, CD32-PE, CD11b-PC5 conjugates (Beckman Coulter International SA, France). Analysis of the obtained data demonstrated that NGs in healthy adults are represented by the major subset of CD64 - CD32 + CD16 + CD11b + NG and the minor subset of СD64 + CD32 + CD16 + CD11b + NG with different expression density of membrane molecules. Minor subset СD64 + CD16 + CD32 + CD11b + NG significantly increased under the influence of dsRNA, fMLP and dsRNA+fMLP in comparison with intact samples. Comparative analysis of the mono-influence of immunotropic substances revealed their multidirectional effects on the surface receptor molecules CD16, CD32 and the unidirectional effect, but of different intensities on CD11b, both in the major and minor subsets. Preincubation with dsRNA with the addition of fMLP in the study group revealed the effects of the joint stimulating effect of substances on the surface receptor levels of both subsets of NG. We created an experimental model of viral-bacterial co-infection in the in vitro system using fMLP and dsRNA and established variation of phenotype transformation of CD64 - CD32 + CD16 + CD11b + NG and СD64 + CD32 + CD16 + CD11b + NG subsets. This model can be used to evaluate the transformation of other subsets NG phenotype, to study the functional activity of NG, the features of the formation of NET, and the effect of various immunotropic substances on NG.