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2.
J Gen Virol ; 95(Pt 7): 1504-1509, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24739273

RESUMO

Although many cells undergo transformation, few actually develop into tumours, due to successful mechanisms of immunosurveillance. To investigate whether an infectious agent may play a role in this process, the growth of a plasmacytoma was investigated in mice infected by lactate dehydrogenase-elevating virus. Acutely infected animals were significantly protected against tumour development. The mechanisms responsible for this protection were analysed in mice deficient for relevant immune cells or molecules and after in vivo cell depletion. This protection by viral infection correlated with NK cell activation and with IFN-γ production. It might also be related to activation of NK/T-cells, although this remains to be proven formally. Therefore, our results indicated that infections with benign micro-organisms may protect the host against cancer development, through non-specific stimulation of the host's innate immune system and especially of NK cells.


Assuntos
Células Matadoras Naturais/imunologia , Vírus Elevador do Lactato Desidrogenase/imunologia , Vírus Oncolíticos/imunologia , Plasmocitoma/imunologia , Plasmocitoma/prevenção & controle , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout
3.
J Gen Virol ; 90(Pt 2): 442-447, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19141454

RESUMO

Gamma interferon (IFN-gamma) plays a major role in the protection against lethal infection with mouse hepatitis virus A59. IFN-gamma production reaches a maximum level 2 days after viral inoculation, especially in liver immune cells. Among these cells, natural killer cells are the major producers of this cytokine. Transfer experiments indicated that the protective role of IFN-gamma is mediated through a direct effect on cells targeted by the virus rather than through indirect activation of T lymphocytes.


Assuntos
Infecções por Coronavirus/imunologia , Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Vírus da Hepatite Murina/patogenicidade , Animais , Interferon gama/biossíntese , Interferon gama/sangue , Fígado/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Receptores de Interferon/deficiência , Linfócitos T/imunologia , Fatores de Tempo , Receptor de Interferon gama
4.
Immunology ; 125(4): 535-40, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18492055

RESUMO

CD66a (CEACAM1), an adhesion molecule that has regulatory function on T lymphocytes, was found to be expressed on a minority of mouse natural killer (NK) cells, especially in the liver. CD66a expression on NK cells depended on their differentiation stage, with highest levels on immature CD49b(-)NK cells. Expression of CD66a on NK cells was strongly enhanced by in vitro activation with interleukin-12 (IL-12) and IL-18. However, in vivo NK cell stimulation by infection with lactate dehydrogenase-elevating virus did not lead to strong CD66a expression, even on activated interferon--gamma-producing NK cells. These results indicate that CD66a expression is differently regulated, depending on the NK cell activation pathway, which may lead to distinct regulatory mechanisms of the functional subpopulations of these cells.


Assuntos
Antígenos CD/análise , Moléculas de Adesão Celular/análise , Células Matadoras Naturais/imunologia , Fígado/imunologia , Animais , Antígenos Ly/análise , Infecções por Arterivirus/imunologia , Feminino , Citometria de Fluxo , Integrina alfa2/análise , Interferon gama/análise , Vírus Elevador do Lactato Desidrogenase , Fígado/virologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Subfamília B de Receptores Semelhantes a Lectina de Células NK/análise , Especificidade da Espécie
5.
J Gen Virol ; 88(Pt 11): 3063-3066, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17947531

RESUMO

Two distinct pathways of gamma interferon (IFN-gamma) production have been found in mice infected with lactate dehydrogenase-elevating virus. Both pathways involve natural killer cells. The first is mostly interleukin-12-independent and is not controlled by type I interferons. The second, which is suppressed by type I interferons, leads to increased levels of IFN-gamma production and requires the secretion of interleukin-12. This regulation of IFN-gamma production by type I interferons may help to control indirect pathogenesis induced by this cytokine.


Assuntos
Interferon gama/biossíntese , Células Matadoras Naturais/imunologia , Vírus Elevador do Lactato Desidrogenase/imunologia , Redes e Vias Metabólicas , Animais , Regulação da Expressão Gênica , Interferon Tipo I/imunologia , Interleucina-12/imunologia , Camundongos
7.
Toxicol Appl Pharmacol ; 206(3): 321-33, 2005 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16039943

RESUMO

Gentamicin accumulates in lysosomes and induces apoptosis in kidney proximal tubules and renal cell lines. Using LLC-PK1 cells, we have examined the concentration- and time-dependency of the effects exerted by gentamicin (1-3 mM; 0-3 days) on (i) lysosomal stability; (ii) activation of mitochondrial pathway; (iii) occurrence of apoptosis (concentrations larger than 3 mM caused extensive necrosis as assessed by the measurement of lactate dehydrogenase release). Within 2 h, gentamicin induced a partial relocalization [from lysosomes to cytosol] of the weak organic base acridine orange. We thereafter observed (a) a loss of mitochondrial membrane potential (as from 10 h, based on spectrophotometric and confocal microscopy using JC1 probe) and (b) the release of cytochrome c from granules to cytosol, and the activation of caspase-9 (as from 12 h; evidenced by Western blot analysis). Increase in caspase-3 activity (assayed with Ac-DEVD-AFC in the presence of z-VAD-fmk]) and appearance of fragmented nuclei (DAPI staining) was then detected as from 16 to 24 h together with nuclear fragmentation. Gentamicin produces a fast (within 4 h) release of calcein from negatively-charged liposomes at pH 5.4, which was slowed down by raising the pH to 7.4, or when phosphatidylinositol was replaced by cardiolipin (to mimic the inner mitochondrial membrane). The present data provide temporal evidence that gentamicin causes apoptosis in LLC-PK1 with successive alteration of the permeability of lysosomes, triggering of the mitochondrial pathway, and activation of caspase-3.


Assuntos
Apoptose/efeitos dos fármacos , Gentamicinas/toxicidade , Lisossomos/metabolismo , Mitocôndrias/fisiologia , Animais , Caspase 3 , Caspase 9 , Caspases/biossíntese , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Gentamicinas/química , Concentração de Íons de Hidrogênio , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Rim/citologia , Rim/efeitos dos fármacos , Rim/ultraestrutura , Células LLC-PK1 , Bicamadas Lipídicas/química , Lipossomos/química , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/metabolismo , Necrose , Permeabilidade , Suínos , Fatores de Tempo
8.
Blood ; 104(7): 2102-6, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15205264

RESUMO

Antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of immune thrombocytopenic purpura (ITP). However, because antigenic mimicry implies epitope similarities between viral and self antigens, it is difficult to understand how widely different viruses can be involved by this sole mechanism in the pathogenesis of ITP. Here, we report that in mice treated with antiplatelet antibodies at a dose insufficient to induce clinical disease by themselves, infection with lactate dehydrogenase-elevating virus (LDV) was followed by severe thrombocytopenia and by the appearance of petechiae similar to those observed in patients with ITP. A similar exacerbation of antiplatelet-mediated thrombocytopenia was induced by mouse hepatitis virus. This enhancement of antiplatelet antibody pathogenicity by LDV was not observed with F(ab')2 fragments, suggesting that phagocytosis was involved in platelet destruction. Treatment of mice with clodronate-containing liposomes and with total immunoglobulin G (IgG) indicated that platelets were cleared by macrophages. The increase of thrombocytopenia triggered by LDV after administration of antiplatelet antibodies was largely suppressed in animals deficient for gamma-interferon receptor. Together, these results suggest that viruses may exacerbate autoantibody-mediated ITP by activating macrophages through gamma-interferon production, a mechanism that may account for the pathogenic similarities of multiple infectious agents.


Assuntos
Autoanticorpos , Plaquetas/imunologia , Vírus Elevador do Lactato Desidrogenase/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/virologia , Animais , Anticorpos/química , Anticorpos Monoclonais/química , Doenças Autoimunes/virologia , Plaquetas/metabolismo , Fragmentos de Imunoglobulinas , Imunoglobulina G/química , Interferon gama/metabolismo , L-Lactato Desidrogenase/metabolismo , Lipossomos/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Nus , Fagocitose , Contagem de Plaquetas , Baço/citologia
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