Том 40, № 4 (2023)

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The main causes of HUS are infections caused by Shiga toxin-producing bacteria: hemorrhagic Escherichia coli and Shigella dysenteriae type 1. They account for up to 90% of all cases of HUS. The remaining 10% represent a heterogeneous group of diseases collectively referred to as atypical HUS. The pathogenesis of most cases of atypical HUS is based on congenital or acquired disorders in the complement system. Over the past decades, evidence has accumulated that, in addition to E. coli and Sh. dysenteriae type 1, a wide variety of bacterial and viral infections, including the pathogens of pneumonia Streptococcus pneumoniae, immunodeficiency virus, H1N1 influenza, and a new coronavirus infection, can cause the development of HUS. In particular, infectious diseases act as the main cause of recurrence of atypical HUS. This review presents summarized data from recent studies, indicating that in various types of infectious HUS, disturbances in the complement system are a key pathogenetic factor. The links in the complement system are considered, the dysregulation of which in bacterial and viral infections can lead to complement hyperactivation with subsequent damage to the microvascular endothelium and the development of acute renal failure.

We have studied the process of electroporation of bilayer lipid membranes (BLMs) from dioleoylphosphatidylcholine (DOPC). We obtained experimental data on the average lifetime of the membrane as a function of applied voltage in the range of 200–375 mV. The analysis of the data obtained showed that the dependence is nonmonotonic and cannot be described in terms of the classical theory of electroporation. These results are consistent with modern models of the process of through conductive pores formation in a membrane. The above models imply a complex pore energy profile and its dependence on membrane tension and external electric field. Thus, we have shown that the classical theory of electroporation does not satisfy the experimentally observed dependencies of the average membrane lifetime on the applied potential difference and requires further refinement.

One of the main stages of infectious process, which mostly determines the course and outcome of the disease, is the initial contact of the pathogen with the host cells. The lipopolysaccharide as a component of the outer membrane is crucially involved in the interaction between Gram-negative bacteria and immunocompetent host cells. It triggers immune reactions by interaction with specific receptors, mainly CD14 and TLR4. The aim of this work was to quantify the force characteristics of the interaction of Yersinia pestis EV lipopolysaccharide with CD14 and TLR4 receptors on the surface of mouse macrophages J774 by atomic force microscopy. Lipopolysaccharide was extracted from Y. pestis cells (vaccine strain EV) grown at 27°С. The expression of receptors on the cell surface was evaluated by fluorescent and confocal microscopy. Using monoclonal antibodies against CD14 and TLR4 receptors, force spectroscopy was used to estimate the force characteristics of the interaction between lipopolysaccharide on the cantilever surface and J774 macrophages immobilized on a glass substrate. The conditions for immobilization of J774 macrophages on glass were developed that allowed scanning the cell surface and estimating the adhesion force of target antigens to the cells. Incubation of macrophages in solutions with monoclonal antibodies against CD14 and TLR4 receptors caused a decrease in the major force characteristics of the interaction in the J774 macrophage – Y. pestis lipopolysaccharide system compared to the system containing untreated macrophages. A similar effect was observed after pretreatment of the cells with a solution containing the same lipopolysaccharide without monoclonal antibodies. The results show the ability of the Y. pestis lipopolysaccharide chemically bound to the cantilever to interact with CD14 and TLR4 receptors on the macrophage surface.