Precise location of IL-18 in cell and tissue elements of the atherosclerotic lesions in humans and its role in destabilization of the atherosclerotic plaque were detected. The data suggested a hypothesis on indirect involvement of IL-18 in destruction of the elastic and collagen fibers in an unstable plaque due to this cytokine capacity to induce the production of IFN-γ in T cells and macrophages, this eventually leading to inhibition of collagen and elastin synthesis in smooth muscle cells of the vascular wall and to loosening of the plaque cap.

Immunomorphological analysis of renal tissue from rabbits immunized with group A streptococci differing in the expression of IgG Fc-binding proteins showed that only IgG Fc-positive streptococci induced destructive degenerative changes in the kidneys classified as membranous proliferative glomerulonephritis with symptoms of fibroplastic glomerulonephritis. These morphological changes in renal tissue are comparable to changes in patients with acute poststreptococcal glomerulonephritis. Depositions of IgG and C3 complement component on the basal membrane of renal glomeruli and secretion of antiinflammatory cytokines IL-113, IL-6, and TNF-~ by mesangial cells were revealed. No destructive changes were found in the kidneys of rabbits immunized with IgG Fc-negative streptococcus strain or isogenic mutant completely devoid of genes responsible for the expression of IgG Fc-binding proteins. Thus streptococcal IgG Fc-binding proteins determine the development of experimental glomerulonephritis in rabbits. Key Words: group A streptococci; IgG Fc-receptors; isogenic mutant; anti-IgG; experimental glomerulonephritisSerogroup A streptococci induce a wide spectrum of diseases in humans, some of which are acute infections (tonsillitis, pharyngitis, scarlet fever, suppurative lesions of the skin, necrotic fasciitis, sepsis, toxic shock syndrome), others are chronic (rheumatic fever, poststreptococcal glomerulonephritis).M-protein and hyaluronic capsule were for a long time believed to be the main factors responsible for pathogenicity of serogroup A streptococci and their resistance to phagocytosis in vivo [7,14]. However, after the discovery of streptococcal ability to react with human and mammalian blood proteins, primarily with IgG Fc-fragment, special attention was paid to investigation of the receptor proteins and their role in the microbe biology and its interactions with the host.

Comparative study of the walls of the aorta, coronary artery, and a. basilaris detected for the first time intra- and extracellular depositions of Chlamydia pneumoniae in unstable atherosclerotic plaques. No chlamydia were detected in the intima of normal sites of the vascular wall and just negligible levels thereof in stable atherosclerotic plaques. An unstable plaque with intra- and extracellular colonies was characterized by infiltration of the cap and intima adjacent to the atheromatous core with mononuclear cells, primarily T cells. These data suggested that Chlamydia pneumoniae could play an important role in the development of immunoinflammatory processes in the vascular wall and promote destabilization and progressive development of atherosclerotic plaques in humans.

The pathogenesis of poststreptococcal glomerulonephritis (PSGN), a major complication of acute infections caused by group A streptococci (GAS) remains unclear. Several theories, based on the role of certain streptococcal virulence factors, as well as immunological mimicry between GAS and renal tissue, have been proposed. Earlier, we reported that many virulent clinical GAS isolates showing confirmed nephritogenic activity were capable of nonimmune Fc binding of monomeric or aggregated IgG. Moreover, a rabbit model of PSGN allowed to obtain findings regarding a crucial role of streptococcal IgG Fc binding proteins belonging to the M family surface proteins, in the onset of PSGN. Rabbits injected with inactivated IgGFcBP-positive streptococci, acquired changes in the renal tissue with deposited IgG and complement C3, as well as signs of immune inflammation characteristic for human PSGN. Also, it was shown that the induction of experimental glomerulonephritis could be inhibited after normal IgG or its purified Fc fragments were inoculated at early stages of the process. The data obtained in rabbits injected with group A streptococcal type M60 also showed pathogenic functions of the IgA Fc-binding proteins of GAS. The aim of the study was to examine inhibiting activity of the purified rabbit IgG Fc fragments on the manifestations of glomerulonephritis induced by S. pyogenes strains capable of binding diverse forms of immunoglobulins such native IgG, immune complexes, and IgA.Materials and methods. GAS strains of emml, emml2 and emm60 genotypes were used to induce PSGN or IgA-nephropa-thy in rabbits. Fc fragments derived from rabbit IgG were obtained by enzymatic digestion and purified by affinity chromatography on a protein G-sepharose FF column. Immunomorphological changes of renal tissue were estimated by morphometric analysis.Results. In the present study, using the rabbit model, we revealed pathological changes of different intensity and localization in the renal tissue. For streptococci of the emm1 and emm12 genotypes, PSGN was characterized by deposition of IgG or IgG-anti-IgG immune complexes within the basal glomerular membrane. Morphological changes were evaluated as a membranous-proliferative glomerulonephritis. Meanwhile, IgA-glomerulonephritis is characterized by deposition of IgA in mesangial cells of glomeruli, leading to the mesangial-proliferative glomerulonephritis or IgA-nephropathy. Intravenously administered purified Fc fragments derived from normal rabbit IgG varied in effects on pathological processes: (i) IgG Fc fragments of fully inhibited development of the PSGN induced by IgG Fc binding strain of emml genotype, (ii) IgG Fc fragments of partially reverted changes caused by the emm12 genotype strain, which was binding only to immune complexes, and (iii) had no effects on pathological changes caused by the emm60 genotype GAS strain, which was binding only IgA.Conclusion. The data obtained point and emergence of differences in mechanisms of renal lesions development at glomerulonephritis, depending on the emm genotype of GAS strain. In addition, it also confirmed GAS-derived involvement for various IgFc-receptor proteins in the pathology. Further studies on potential prophylactic or curative effects of IgG Fc fragments in PSGN should therefore be of interest. The findings might suggest a new therapeutic approach for non-suppurative poststreptococcal diseases.