RESUMO
In CBA mice infected with influenza viruses A/H1N1/California/04/2009 and A/H5N1/Goose/Krasnoozerskoye/627/05 in a dose of 10 MLD50, the mechanisms of death of pulmonary alveolocytes over 10 postinfection days were studied by light microscopy, immunohistochemistry, and morphometry. In mice infected with A/H1N1, alveolocytes died predominantly via necrosis, while apoptosis mostly employed the mitochondrial pathway. In mice infected with A/H5N1, apoptosis was the dominant mechanism of alveolocyte death proceeded via membrane receptor signaling followed by switching to FAS-mediated pathway via activation of FADD, the apoptotic signal transduction protein.
Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Virus da Influenza A Subtipo H5N1/patogenicidade , Pulmão/citologia , Alvéolos Pulmonares/virologia , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Camundongos , Camundongos Endogâmicos CBA , Infecções por Orthomyxoviridae/virologia , Alvéolos Pulmonares/citologiaRESUMO
Light microscopy, immunohistochemistry, and morphometric examinations established that cell death in lung granulomas of BCG-infected mice resulted mainly from activation of receptor-mediated apoptosis, which did not prevent the persistence of the causative agent in macrophages of the granulomas and promoted the formation of pronounced fibrosis in granulomas and pulmonary interstitium.
Assuntos
Vacina BCG/efeitos adversos , Granuloma/induzido quimicamente , Granuloma/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Imuno-Histoquímica , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
We analyzed cytokine profile of pulmonary macrophages in mice infected with highly pathogenic influenza A/H5N1 virus after preventive injections of oxidized dextran. Light microscopy, immunohistochemistry, and morphometric examinations showed that preventive injections of oxidized dextran led to more effective virus elimination, modulation of the proinflammatory cytokine response, and host antiviral response and reduce animal mortality. Our findings allow recommending oxidized dextran for further studies in order to create a vaccine with antiviral and adjuvant potencies.
Assuntos
Antivirais/uso terapêutico , Dextranos/uso terapêutico , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/patogenicidade , Macrófagos Alveolares/virologia , Animais , Antivirais/química , Dextranos/química , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/patogenicidade , Masculino , Camundongos , Óxido Nítrico Sintase/metabolismo , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/prevenção & controle , OxirreduçãoRESUMO
Influenza A/H1N1 A/Tomsk/13/2010 virus registered in Siberia in 2010 proved to be an extremely pathogenic strain. Dynamic study of the topology of this influenza virus strain in the lungs, liver, kidneys, lymph nodes, and great vessels of infected mice was carried out. Influenza A virus was detected by immunohistochemical methods in cells of different histogenesis in all the studied organs throughout the observation period (days 1-30 postinfection), which indicated effective replication and long persistence of influenza A/H1N1 A/Tomsk/13/2010 virus in mammalian cells.
Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Rim/virologia , Pulmão/virologia , Linfonodos/virologia , Infecções por Orthomyxoviridae/patologia , Animais , Rim/patologia , Pulmão/patologia , Linfonodos/patologia , Camundongos , Infecções por Orthomyxoviridae/virologia , Sibéria , Replicação ViralRESUMO
Intranasal infection of outbred male mice with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus led to high (85%) mortality of animals. Morphological studies of liver specimens showed destructive changes in the parenchyma (93.5% hepatocytes), caused by long persistence of the virus in the liver. The virus persistence was conjugated with activation of cellular immunity, manifesting by an increase in the counts of cells with high expression of proinflammatory cytokines (TNF-α) and lysosomal enzymes (lysozyme, cathepsin D). Injections of oxidized dextran 3 and 1 days before infection reduced mortality and 2-fold attenuated destructive changes in the liver, presumably due to prevention of virus penetration into the target cells, modulation of immune reactions, and stimulation of reparative plastic processes.
Assuntos
Dextranos/farmacologia , Virus da Influenza A Subtipo H5N1 , Fígado/efeitos dos fármacos , Fígado/fisiologia , Infecções por Orthomyxoviridae/prevenção & controle , Regeneração/efeitos dos fármacos , Animais , Catepsina D/metabolismo , Citocinas/metabolismo , Técnicas Histológicas , Imuno-Histoquímica , Fígado/lesões , Masculino , Camundongos , Muramidase/metabolismo , Tamanho do Órgão , Regeneração/fisiologiaRESUMO
Oxidized dextran is suggested for prevention of infection induced by influenza A/H5N1 viruses, methods of its use and doses are determined. Two intravenous injections of dextran 3 and 1 days before experimental infection of outbred mice by influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus resulted in a high preventive dose-dependent effect: the mean lifespan was 25% prolonged, the mortality decreased 3-fold.
Assuntos
Antivirais/uso terapêutico , Dextranos/uso terapêutico , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Animais não Endogâmicos , Antivirais/farmacologia , Dextranos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Camundongos , Infecções por Orthomyxoviridae/virologia , OxirreduçãoRESUMO
Generalized BCG-induced granulomatous was simulated in BALB/c male mice. The number of tuberculous granulomas in the liver and their size as well as the number of hepatocytes showing vacuolar degeneration increased from day 3 to 180 postinfection. Necrotic changes in hepatocytes were most pronounced at the acute phase of inflammation (days 3 to 30). Proliferative processes in the liver parenchyma in the experimental group were less marked than in the control. Increased content of collagen fibers in the liver was determined by excessive collagen synthesis in necrotic areas as well as increased amount of granulomas and fibroblasts. Enhanced proliferative and fibroplastic activity of fibroblasts in granulomas and liver parenchyma was evidently determined by activated granuloma macrophages. These shifts determined changes in the liver content of hydroxyproline during the acute and chronic periods of the disease.
Assuntos
Granuloma/patologia , Cirrose Hepática/patologia , Fígado/patologia , Tuberculose Gastrointestinal/patologia , Doença Aguda , Animais , Vacina BCG/efeitos adversos , Doença Crônica , Colágeno/química , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Granuloma/induzido quimicamente , Granuloma/complicações , Granuloma/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Hidroxiprolina/metabolismo , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tuberculose Gastrointestinal/induzido quimicamente , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/metabolismoRESUMO
The protective effect of water-soluble TS-13 monophenol inducing the antioxidant-responsive element (ARE) system was studied on the models of acute inflammation. Intragastric administration of TS-13 to rats significantly reduced the severity of acute aseptic inflammation induced by intravenous injection of zymosan particles: granulocyte blood count and volume density of infiltrates in the liver decreased on day 3, spontaneous production of activated oxygen metabolites and respiratory burst in blood granulocytes decreased on days 2 and 3. A single dose of TS-13 improved survival of mice with endotoxin shock induced by intraperitoneal injection of E. coli LPS. These results confirmed high anti-inflammatory activity of TS-13.
Assuntos
Anti-Inflamatórios/farmacologia , Elementos de Resposta Antioxidante/efeitos dos fármacos , Inflamação/tratamento farmacológico , Ácidos Tiossulfônicos/farmacologia , Animais , Elementos de Resposta Antioxidante/fisiologia , Granulócitos/fisiologia , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Explosão Respiratória/fisiologia , ZimosanRESUMO
In generalized BCG granulomatosis, fibrosis starts early (on day 3) and not only around the granulomas, but also in the organs. The severity of organ fibrosis is apparently determined by the concentration of granulomas, in particular their macrophages inducing proliferation of fibroblasts in organs and granulomas as well as activation of fibrogenesis. On day 30 after infection, the degree of fibrosis in the lungs was by 6 times higher than in the liver. The increase in hydroxyproline concentration in organs in early period of infection was determined by acute stress, while on day 30 it resulted from its enhanced synthesis by granuloma fibroblasts and resident fibroblasts in organs.
Assuntos
Granuloma/metabolismo , Granuloma/patologia , Hidroxiprolina/análise , Fígado/patologia , Pulmão/patologia , Mycobacterium bovis , Animais , Proliferação de Células , Fibroblastos , Fibrose , Granuloma do Sistema Respiratório/metabolismo , Granuloma do Sistema Respiratório/microbiologia , Granuloma do Sistema Respiratório/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse FisiológicoRESUMO
C57Bl/6 mice were intranasally infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05. The mortality rate of animals reached 70% on day 14 of the disease. The lungs of animals were characterized by necroses, destruction of vessels, hemorrhagic and thrombotic complications, edematous syndrome, and early fibrosis of the interstitium. On days 6-10 after infection, fibrosis was found in the zones of postnecrotic inflammatory infiltration. The expression of lysozyme and myeloperoxidase by pulmonary macrophages was initially increased, but decreased on day 10 of the study. The number of cathepsin D-expressing macrophages was elevated up to the 10th day of examination.
Assuntos
Virus da Influenza A Subtipo H5N1 , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Animais , Catepsina D/metabolismo , Modelos Animais de Doenças , Proteína de Domínio de Morte Associada a Fas/metabolismo , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Interleucina-6/metabolismo , Pulmão/imunologia , Pulmão/virologia , Macrófagos Alveolares/citologia , Macrófagos Alveolares/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Muramidase/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Peroxidase/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Oxidized dextran (60 kDa) exerted a pronounced preventive effect in laboratory mice infected with avian influenza subtype H5N1 A/Goose/Krasnoozerskoye/627/05 virus, which manifested in a significant increase in mouse lifetime (by 24.4%) and a decrease in mortality rate (3.3-fold). This was probably related to significant alleviation of pathological changes in the lungs and severity of hemodynamic and inflammatory complications and early fibrosis [corrected].
Assuntos
Dextranos/farmacologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Pulmão/patologia , Infecções por Orthomyxoviridae/patologia , Animais , Dextranos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/virologia , Masculino , Camundongos , Infecções por Orthomyxoviridae/virologiaRESUMO
Structural changes in the brain of outbred mice were studied after infection with influenza A/H5N1 strain isolated in the Novosibirsk region. High mortality was observed after intranasal infection. Examination of brain specimens revealed vasculopathies with thrombosis of the microcirculatory vessels, pericellular and perivascular edema with multifocal ischemic necrosis, hyperplasia of glial cells, caspase-dependent apoptosis of neurons caused by the cytopathic effect of the virus, and hypercytokinemia.
Assuntos
Encéfalo/patologia , Encéfalo/virologia , Virus da Influenza A Subtipo H5N1/fisiologia , Infecções por Orthomyxoviridae/patologia , Animais , Citocinas/sangue , Masculino , CamundongosRESUMO
Intravenous infection of chicken with H5N1 avian influenza virus (strain A/Gs/Krasnoozerskoye/627/05) causes rapid lethal outcome. Pathomorphological study of bird viscera showed manifestations of disseminated intravascular coagulation syndrome, generalized inflammatory reaction, and wide-scale necrobiotic changes in tissues.
Assuntos
Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Aviária/patologia , Influenza Aviária/virologia , Vísceras/patologia , Vísceras/virologia , Animais , Encéfalo/patologia , Encéfalo/virologia , Embrião de Galinha , Galinhas , Rim/patologia , Rim/virologia , Pulmão/patologia , Pulmão/virologia , Baço/patologia , Baço/virologiaRESUMO
Intranasal infection of male outbred rats with isolate of influenza A virus subtype H5N1 (A/Gs/Krasnoozerskoye/627/05) from the Novosibirsk region was followed by high mortality of experimental animals. Morphological study of liver samples revealed subtotal destructive changes in the liver parenchyma (proteinosis and centrolobular necroses), which was related to hemodynamic disorders and cytokine dysregulation. The decrease in reparative activity of hepatocytes was probably followed by hepatocellular failure and contributed to high mortality rate from this infection (up to 85%).