RESUMO
Switched CD19-positive memory B cells purified from mice with chronic immune response against Thalassophrynenattereri venom proteins were cultured with venom or cytokines. Our results confirm the existence of a hierarchic process of differentiation: activated memory B cells progressively acquire increasing levels of CD138 and decreasing levels of CD45R/B220 to finally arrive at ASC with B220(neg) phenotype, which are IgG1-secreting cells. Only Bmem from peritoneal cavity or bone marrow of VTn immunized mice presented the capacity to generate ASC functionally active. IL-17A or IL-21/IL-23/IL-33 improves the ability of venom to induce intracellular IgG of peritoneal derived-ASC. Cognate stimulation with venom and IL-17A is sufficient to down-regulate the expression of CD45R/B220. BAFF-R is up-regulated in splenic or medullar derived-ASC stimulated by venom, CpG or cytokines. Only splenic derived-ASC up-regulate Bcl-2 expression after CpG or the combination of IL-21/IL-23/IL-33 stimulation. Finally, the activation of ASC for IgG1 secretion is triggered by venom proteins in peritoneal cavity and by IL-17A in medullar niche. These results show the importance of the integration of signals downstream of BCR and IL17-A receptors in modulating ASC differentiation, focusing in the microenvironment niche of their generation.
Assuntos
Células Produtoras de Anticorpos/citologia , Antígenos/imunologia , Diferenciação Celular/imunologia , Interleucina-17/metabolismo , Transdução de Sinais , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/metabolismo , Antígenos CD19/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Diferenciação Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Venenos de Peixe/imunologia , Imunoglobulina G/biossíntese , Memória Imunológica/efeitos dos fármacos , Interleucina-23/farmacologia , Interleucinas/farmacologia , Antígenos Comuns de Leucócito/metabolismo , Contagem de Linfócitos , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Baço/citologia , Receptor Toll-Like 9/metabolismoRESUMO
Alternanthera tenella Colla extracts are used in Brazilian traditional folk medicine to treat a variety of infectious diseases as well as inflammation and fever. In this work, the immunomodulatory, anti-inflammatory and potential toxic effects of cold (CAE) and hot (HAE) aqueous extracts of A. tenella were investigated in vivo. In addition, we analyzed the phytochemical properties of both extracts. BALB/c mice were immunized in vivo with sheep red blood cells and concomitantly inoculated intraperitoneally (i.p.) with each extract (50, 100 or 200 mg/kg). Specific antibody-producing cells were enumerated using plaque-forming cell assays (PFC) and anti-SRBC IgG and IgM serum levels were measured via enzyme-linked immunosorbent assay. Body and lymphoid organ weights were determined after treatments in order to evaluate toxic effects. Carrageenan-induced paw edema was employed to investigate anti-inflammatory activity in mice inoculated i.p. with CAE or HAE (200 or 400 mg/kg). Phytochemical screening was performed using spectrometric and chromatographic approaches and revealed that CAE possessed higher tannin and flavonoid levels than HAE. PFC numbers were increased after treatment with CAE (100 mg/kg) four days after immunization, as were the serum antibody titers after four and seven days, suggesting immunostimulatory activity through modulation of B lymphocyte functions. Body and organ weights did not show major changes, suggesting that extracts administered to mice did not induce significant toxicity. Both extracts had significant anti-inflammatory activity in the paw edema assay. These results suggested that aqueous extracts from A. tenella contained several chemical compounds that possess positive and/or negative modulator effects on the immune system, which appeared to correlate with tannin and flavonoid levels in those extracts. In summary, these studies provide important insight into the biological activities of A. tenella.
Assuntos
Amaranthaceae/química , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carragenina , Temperatura Baixa , Edema/induzido quimicamente , Ensaio de Imunoadsorção Enzimática , Temperatura Alta , Linfonodos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacosRESUMO
Alternanthera tenella Colla extracts are used in Brazilian traditional folk medicine to treat a variety of infectious diseases as well as inflammation and fever. In this work, the immunomodulatory, anti-inflammatory and potential toxic effects of cold (CAE) and hot (HAE) aqueous extracts of A. tenella were investigated in vivo. In addition, we analyzed the phytochemical properties of both extracts. BALB/c mice were immunized in vivo with sheep red blood cells and concomitantly inoculated intraperitoneally (i.p.) with each extract (50, 100 or 200 mg/kg). Specific antibody-producing cells were enumerated using plaque-forming cell assays (PFC) and anti-SRBC IgG and IgM serum levels were measured via enzyme-linked immunosorbent assay. Body and lymphoid organ weights were determined after treatments in order to evaluate toxic effects. Carrageenan-induced paw edema was employed to investigate anti-inflammatory activity in mice inoculated i.p. with CAE or HAE (200 or 400 mg/kg). Phytochemical screening was performed using spectrometric and chromatographic approaches and revealed that CAE possessed higher tannin and flavonoid levels than HAE. PFC numbers were increased after treatment with CAE (100 mg/kg) four days after immunization, as were the serum antibody titers after four and seven days, suggesting immunostimulatory activity through modulation of B lymphocyte functions. Body and organ weights did not show major changes, suggesting that extracts administered to mice did not induce significant toxicity. Both extracts had significant anti-inflammatory activity in the paw edema assay. These results suggested that aqueous extracts from A. tenella contained several chemical compounds that possess positive and/or negative modulator effects on the immune system, which appeared to correlate with tannin and flavonoid levels in those extracts. In summary, these studies provide important insight into the biological activities of A. tenella.
Assuntos
Animais , Masculino , Camundongos , Amaranthaceae/química , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Células Produtoras de Anticorpos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carragenina , Temperatura Baixa , Ensaio de Imunoadsorção Enzimática , Edema/induzido quimicamente , Temperatura Alta , Linfonodos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacosRESUMO
BACKGROUND: Hyperglycemia induces protein glycation, disturbing its function, additionally, the glycated products (AGEs) induce by themselves proinflammatory cytokine release that are responsible for insulin resistance. Glycine has been successfully used in diabetic patients to competitively reduce hemoglobin glycation. OBJECTIVES: To assess hyperglycemia impact on the immune response and to evaluate if it is possible to reverse it by means of glycine administration. MATERIAL AND METHODS: Streptozotocin-induced diabetic rats, with and without glycine administration were challenged with sheep red blood cells, and specific antibody producing cells were accounted. Normal rats were challenged as controls. RESULTS: Induced diabetes modifies significantly the humoral immune response capacity versus sheep red blood cells. Also, glycine administration prevents against this deleterious effect. CONCLUSIONS: Glycine could be an important therapeutic resource among diabetics to avoid the characteristic immunodeficiencies of this disease.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Diabetes Mellitus Experimental/imunologia , Glicina/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/imunologia , Glicemia/análise , Diabetes Mellitus Experimental/complicações , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/imunologia , Hemoglobinas Glicadas/análise , Produtos Finais de Glicação Avançada/análise , Glicina/farmacologia , Síndromes de Imunodeficiência/etiologia , Masculino , Ratos , Ratos Wistar , Ovinos , EstreptozocinaRESUMO
Female CBi mice subjected to multiple exposures to halothane inhalation anesthesia before mating were investigated for the potential effects of such intervention on a specific antibody response mounted by them and their offspring. An assessment of the toxicologic and reproductive performance of female mice undergoing anesthesia was also performed. Adult female mice received three episodes of halothane anesthesia at weekly intervals. Seventy-two hours after the last dose, mice were subjected to the following procedures: 1) study of the specific humoral immune response to sheep red blood cells (SRBC); 2) hematologic, hepatologic, and histopathologic studies; and 3) mating with syngeneic sires. Halothane-treated females had increased amounts of specific antibody secreting B cells, with liver studies showing evidence of microscopic fatty changes and decreased lipid peroxidation. Anesthesia did not alter reproductive performance but lowered offspring survival. Offspring displayed depressed antibody response after challenge with SRBC at weaning and at 60 d of age. The anti-SRBC antibody response that was found to be enhanced in halothane anesthetized females, seemed to be conversely impaired when studied in the offspring.
Assuntos
Anestésicos Inalatórios/toxicidade , Halotano/toxicidade , Sistema Imunitário/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Contagem de Células Sanguíneas/efeitos dos fármacos , Eritrócitos/imunologia , Feminino , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Baço/imunologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The effects of long-term treatment with sodium valproate (VAL) on humoral immunity (Jerne plaque assay) and the delayed-type hypersensitivity (DTH) response of mice were studied. The resistance of treated animals to bacterial infection was also investigated. Various doses of sodium valproate were administered intraperitoneally (on alternate days) for periods of 1, 3 and 7 weeks. Although treatment for 1 week produced no significant effect, VAL treatment (50 and 150 mg/kg/48 h) for periods of 3 and 7 weeks resulted in enhanced numbers of plaque-forming cells (PFC) per spleen and increased spleen weights (after 3 weeks treatment). In contrast, VAL pretreatment of spleen cells in vitro was without effect. Also, no effect of VAL on DTH was observed after 1 or 3 weeks treatment (150 mg/kg/48 h).
Assuntos
Sistema Imunitário/efeitos dos fármacos , Ácido Valproico/farmacologia , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Feminino , Hipersensibilidade Tardia , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Baço/anatomia & histologia , Baço/efeitos dos fármacos , Ácido Valproico/administração & dosagemRESUMO
It is well known that Entamoeba histolytica can cause damage to its host by means of enzymes, cytotoxins and perforins that affect different types of cells. In this work we investigated the effect of different Entamoeba histolytica trophozoites products over the secretion of antibodies by mice Peyer's patches using a reverse hemolytic assay. Results showed that amoebic glycoproteins inhibited the secretion of antibodies by lymphocytes from mice Peyer's patches. In all cases the decrease in antibody secretion was not due to cell death. The molecules responsible for this effect were shown to be high molecular weight immunogenic glycoproteins without enzymatic activity. The fact that amoebic glycoproteins interfere with plasmatic cells function could be another mechanism of evasion of the immune response by Entamoeba histolytica, although we still do not know how these amoebic products cause the inhibition.