The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

Kudaeva, O. T.; Колесникова, О. П.; Гойман, Е. В.; Tkachev, Victor; Volsky, N N; Perminova, Olga; Гаврилова, Е. Д.; Козлов, В. А.

doi:10.5772/22005

Cited by 4 publications

(7 citation statements)

References 140 publications

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“…Chronic GVHD in the semi-allogenic system was induced according to the standard regimen by inoculating splenocytes from DBA/2 mice to B6D2F 1 hybrid mice: 60-70 × 10 6 cells iv twice with an interval of 6 days [3]. The outcome of the immunopathological process in individual animals was determined 3 months after the induction of GVHD by measuring the level of protein in the urine: with proteinuria of 3 mg/ml or more, mice were classified as a Th2dependent variant of GVHD, leading to the formation of glomerulonephritis, in the presence of protein in urine less than 3 mg/ml -to a Th1-dependent variant of the disease.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, it was found that recipients develop two variants of this disease after the induction of chronic GVHD. Th2-dependent response, leading to the formation of glomerulonephritis and Th1dependent -without nephritis, but with severe immunodeficiency [3]. Development of either of such scenarios is determined by the magnitude of Th1/Th2 ratio in individual animals at early stage of chronic GVHD development.…”

Section: Introductionmentioning

confidence: 99%

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FATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVO

et al. 2021

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While conducting numerous studies, including researchers in our laboratory, it was found that Th1/Th2 balance plays an essential role in the regulation of reactions that determine the outcomes of immunopathological processes in both chronic and acute GVHD models. However, the question about activity of which element in the regulatory process during GVHD induction (for example, a receptor or an enzyme) affects the ratio of this balance depends remains open. It has been suggested that the degree of activation of the GPR84 receptor during GVHD induction can significantly affect the host Th1/Th2 balance. And, by assessing this parameter, the direction of development and the intensity of the pathological process can be determined. The aim of this work was to investigate the effect of ligands such as medium-chain fatty acid receptor GPR84 on the Th1/Th2 balance in an experimental model in an in vivo system.Female DBA/2 and hybrids (C57Bl/6 × DBA/2) F1 mouse strains were used in the experiments.The studied ligands of GPR84 were capric and lauric acids, as well as a synthetic ligand 6-OAU. Chronic GVHD in the semi-allogenic system was induced by injecting splenocytes from DBA/2 mice to B6D2F1 hybrid mice: 60-70 × 106 -cells iv twice with an interval of 6 days. The first administration of the GPR84 ligands was performed one hour after the donor cell transfer and then once a day for two weeks.The effect of the study drugs on the course of chronic GVHD was assessed three months after the onset of the experiment.It was shown that the administration of GPR84 ligands to to animals during the induction of chronic GVHD affects the activity of the receptor and the host Th1/Th2 ratio. In the group with the injection of 6-OAU, the number of animals which the immunopathological process developed according to the Th1-dependent variant increased by more than 1.5-fold, compared with the control group. This fact is consistent with the literature data obtained in the in vitro system. Apparently, the effect of a mixture of capric and lauric acids is mediated by some other mechanism, differed from the GPR84 activation. Therefore, further research is required to realize the promising possibility of adjusting immune responses by including certain fatty acids in the diet.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVO

et al. 2021

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“…In previous years, we have studied in detail one of the standard experimental models of SLE, based on the induction of chronic graft-versus-host disease (cGVHD) in the semi-allogeneic system DBA/2 → (C57Bl/6 x DBA/2)F1 [3,5]. It was found that the immunopathological process caused by the transfer of lymphocytes from one of the parental lines to hybrid mice can proceed both according to the Th2dependent developmental variant with the formation of lupus-like immunocomplex glomerulonephritis, and according to the Th1-dependent developmental variant -without nephritis, but with manifestations of severe immunodeficiency.…”

Section: т 25 №mentioning

confidence: 99%

Blood platelets in chronic graft-versus-host disease: association with Th1/Th2 ratio

et al. 2023

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As found in clinical and laboratory studies, platelets not only play a key role in the processes of coagulation and thrombosis, but are also able to actively participate in other pathophysiological processes, including the development of immune reactions. It has been shown that changes in the immune system leading to systemic lupus erythematosus (SLE) are often accompanied by changes in the number of platelets and their activity in the peripheral blood of SLE patients, which correlate with the severity of the clinical manifestations of the disease. Earlier we have studied the standard experimental model of SLE in detail, based on the induction of chronic graft-versus-host disease (cGVHD) in the semi-allogeneic system DBA/2 → (C57Bl/6 x DBA/2)F1. However, the participation of platelets in this immunopathological process has not been studied. There are no data in the literature on the behavior of platelets in cGVHD or on their relationship with the state of Th1/Th2 balance. It can been expected that the platelet count changes according to the development of cGVHD in the used experimental model by analogy with the development of SLE in humans.In the experiments, we used female mice of the DBA/2 strain and (C57Bl/6 × DBA/2)F1 hybrids. Chronic GVHD in a semi-allogeneic system was induced by injecting DBA/2 mouse splenocytes into B6D2F1 hybrid mice: 60-70 × 106 cells intravenously twice with an interval of 6 days. The studied parameters were evaluated three months after the start of the experiment and the formation of lupus-like glomerulonephritis in animals with Th2-dependent cGVHD variant.A decrease in the number of erythrocytes and hemoglobin, a decrease in hematocrit and a parallel increase in the number of reticulocytes in the blood of mice with cGVHD are in good agreement with our earlier conclusion that these animals have autoimmune hemolytic anemia. It was found that, platelets increase significantly with the development of cGVHD unlike other blood cells. Secondary thrombocytosis is observed in the case of the Th2-dependent variant of сGVHD in this model of SLE, while in the group with the Th1-dependent variant of сGVHD, the average number of platelets in the blood does not differ from the control group.

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“…25, № 4 2022, Т. 25, № 4 ной ДНК (внДНК) в группе CКВ нефрит+ почти в 2 раза превышало аналогичный показатель у мышей в группе CКВ нефрит-, однако изменения оказались статистически не достоверны [1,4].…”

Section: динамика внднк в лпс модели воспаленияunclassified

Dynamics of cell-free DNA levels in the in vivo LPS-induced inflammation model

Демченко¹,

Гаврилова²,

Гойман³

et al. 2022

Russian Journal of Immunology

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An increased concentration of extracellular cell free DNA (cfDNA) is a distinctive characteristic of pathologies that mainly occur in acute inflammation (myocardial infarction, sepsis, stroke, trauma). The increase of cfDNA in chronic inflammatory processes, oncological, autoimmune diseases is less significant and is mainly due to aberrant cell death processes. One of such diseases is systemic lupus erythematosus (SLE). It has recently been shown that, in addition to increased cfDNA concentration, the degree of inflammation can reflect the N/L index (neutrophil to lymphocyte ratio), being a simple and informative marker of disease activity in patients with SLE. The aim of the study was to study the dynamics of the level of cfDNA and the N/L index in the model of LPS-induced inflammatory response as observed in intact mice, and their relation to the phenotypic heterogeneity of model SLE. We used female hybrid mice (C57Bl/6xDBA/2) F1 and female DBA/2 mice at the age of 6-8 weeks. LPS of E. coli strain 111: B4 (Sigma) was injected intraperitoneally once at doses of 10 ng, 1 g and 100 g per mouse in PBS. The control group was injected with the appropriate volume of buffer. The TNF-binding domain of the variola virus CRMB protein was used as an inhibitor of TNF, which was administered 30 min before the introduction of LPS. The dynamics of the response to LPS was assessed after 4, 8, 11, 24 hours by the N/L index and the level of cfDNA; at the zero point, the parameters were determined before the introduction of LPS. A day after a single injection of LPS at a dose of 1 g/mouse, a SLE model was induced on the same hybrid mice (double intravenous administration with an interval of 6 days of spleen cells of the DBA/2 line, 60-70 106 cells each). Three months later, with proteinuria of 3 mg/ mL or more, mice were assigned to the SLEnephritis+ group, with a protein of less than 3 mg/mL, to the SLEnephritis- group. Statistical processing of the results was carried out by nonparametric statistics using the MannWhitney test. Differences were considered statistically significant at p 0.05. It was found that the change in the N/L index, as well as the change in the level of cfDNA, depends on the dose of LPS administered. It was shown that the level of cfDNA reaches its maximum after 8 and 11 hours after the introduction of LPS is reliably reduced when using the inhibitor TNF. A retrospective analysis indicates that there is a definite relationship between the response of intact mice to LPS before induction of cGVHD, and their subsequent division into variants of SLEnephritis + and SLEnephritis - in the course of disease development.

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The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

Cited by 4 publications

References 140 publications

FATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVO

FATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVO

Blood platelets in chronic graft-versus-host disease: association with Th1/Th2 ratio

Dynamics of cell-free DNA levels in the in vivo LPS-induced inflammation model

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