RESUMO
Based on a lack of severe phenotype in human immunoglobulin A (IgA) deficiency syndromes, the role of IgA in controlling respiratory and gastrointestinal (GI) infections has not been clearly defined. C57BL/6 and BALB/c mice lacking IgA (IgA(-/-)) were developed and used to address this question. When exposed to a common GI virus, rotavirus, IgA(-/-) mice exhibited a substantial and significant delay in clearance of the initial infection compared with wild-type mice. IgA(-/-) mice excreted rotavirus in stool up to 3 weeks after the initial exposure compared with 10 days observed in wild-type mice. Importantly, IgA(-/-) mice failed to develop protective immunity against multiple repeat exposures to the virus. All IgA(-/-) mice excreted virus in the stool upon re-exposure to rotavirus, whereas wild-type mice were completely protected against re-infection. These findings clearly indicate a critical role for IgA in the establishment of immunity against a GI viral pathogen.
Assuntos
Anticorpos Antivirais/imunologia , Deficiência de IgA/imunologia , Imunoglobulina A/genética , Imunoglobulina A/imunologia , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Imunidade Adaptativa , Animais , Anticorpos Antivirais/sangue , Fezes/virologia , Feminino , Deleção de Genes , Expressão Gênica , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Carga ViralAssuntos
Expressão Gênica , Técnicas Genéticas , Estresse Oxidativo/genética , Oxigênio/toxicidade , Biossíntese de Proteínas , Sequência de Aminoácidos , Animais , Anticorpos , Autorradiografia/métodos , Sequência de Bases , Northern Blotting/métodos , Western Blotting/métodos , Clonagem Molecular , Primers do DNA , Sondas de DNA , DNA Complementar/biossíntese , Eletroforese em Gel Bidimensional/métodos , Eletroforese em Gel de Poliacrilamida/métodos , Expressão Gênica/efeitos dos fármacos , Indicadores e Reagentes , Focalização Isoelétrica/métodos , Dados de Sequência Molecular , Proteínas/análise , RNA/biossíntese , RNA/isolamento & purificação , Espécies Reativas de Oxigênio/farmacologia , Transcrição GênicaRESUMO
In mammalian cells, hydrogen peroxide is known to induce the expression of several genes thought to be important in protection against oxidative stress. Using mRNA differential display, we have identified a novel RNA in hamster HA1 cells that is strongly induced by hydrogen peroxide under conditions where a protective adaptive response occurs. This induction was observed between 1 and 18 h after peroxide treatment, and at an H202 concentration that caused little or no cytotoxicity. Northern blot analysis revealed that this major inducible RNA species, termed adapt15, is 950 bases in size. Two versions of this RNA were found by sequence analysis, differing only by a short trinucleotide stretch. Despite polyadenylation, no large open reading frame was observed. Fractionation studies, however, indicate that adapt15 RNA is primarily located in the cytoplasm, and a significant percentage of it is associated with active translation. adapt15 RNA may act at the level of translation to protect cells against the damaging effect of oxidative stress.