RESUMO
Neutrophils enter the peripheral blood from the bone marrow and die after a short time. Molecular analysis of spontaneous neutrophil apoptosis is difficult as these cells die rapidly and cannot be easily manipulated. We use conditional Hoxb8 expression to generate mouse neutrophils and test the regulation of apoptosis by extensive manipulation of B-cell lymphoma protein 2 (Bcl-2)-family proteins. Spontaneous apoptosis was preceded by downregulation of anti-apoptotic Bcl-2 proteins. Loss of the pro-apoptotic Bcl-2 homology domain (BH3)-only protein Bcl-2-interacting mediator of cell death (Bim) gave some protection, but only neutrophils deficient in both BH3-only proteins, Bim and Noxa, were strongly protected against apoptosis. Function of Noxa was at least in part neutralization of induced myeloid leukemia cell differentiation protein (Mcl-1) in neutrophils and progenitors. Loss of Bim and Noxa preserved neutrophil function in culture, and apoptosis-resistant cells remained in circulation in mice. Apoptosis regulated by Bim- and Noxa-driven loss of Mcl-1 is thus the final step in neutrophil differentiation, required for the termination of neutrophil function and neutrophil-dependent inflammation.
Assuntos
Apoptose , Neutrófilos/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Regulação para Baixo , Proteínas de Homeodomínio/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína bcl-X/metabolismoRESUMO
We tested by electron microscopy 7,530 samples from children admitted to different hospitals in Sofia between February 1981 and February 1986; from these, rotaviruses were found in 725 (9.6%) faecal samples. Electron microscopic analysis of 264 samples from 181 children admitted to the hospital of infectious diseases in Shumen between December 1984 to February 1986 revealed rotaviruses in 120 (66.6%) of the tested children. A part of the samples positive by electron microscopy was tested by ELISA and polyacrylamide gel electrophoresis for rotavirus RNA segment patterns. Rotaviruses with eight different electropherotypes were found in Bulgaria. The seasonal culmination of the rotavirus gastroenteritis in the winter months has been confirmed. Rotavirus antibodies were found in 73% of the sera from 152 children tested.
Assuntos
Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Bulgária , Criança , Pré-Escolar , Métodos Epidemiológicos , Fezes/microbiologia , Gastroenterite/etiologia , Humanos , Lactente , Recém-Nascido , Microscopia Eletrônica , Rotavirus/isolamento & purificação , Estações do AnoAssuntos
Antígenos Virais/imunologia , Diarreia/microbiologia , Infecções por Rotavirus/microbiologia , Rotavirus/imunologia , Bulgária , Diarreia/epidemiologia , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Microscopia Eletrônica , Rotavirus/isolamento & purificação , Rotavirus/ultraestrutura , Infecções por Rotavirus/epidemiologiaAssuntos
Poliomielite/prevenção & controle , Fatores Etários , Formação de Anticorpos , Bulgária , Criança , Pré-Escolar , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/imunologia , Feminino , Humanos , Lactente , Masculino , Poliomielite/epidemiologia , Poliomielite/mortalidade , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio de Vírus Inativado/uso terapêutico , Estações do Ano , Fatores Sexuais , Viroses/epidemiologiaRESUMO
Antigenically distinct rotaviruses, i.e., viruses morphologically identical to conventional rotaviruses by electron microscopy, yet lacking the common group antigen(s) detected by an enzyme-linked immunosorbent assay, were found in 2 of 51 fecal samples from Bulgarian infants with rotavirus gastroenteritis. These antigenically distinct viruses contained 11 segments of double-stranded RNA, but they demonstrated a unique RNA migration profile after electrophoresis of the genome RNA in polyacrylamide gels. This report confirms the presence of a new group of rotaviruses in humans. The significance of these viruses is currently unknown, and specific diagnostic tests must be developed for epidemiological studies to determine their role as human and veterinary pathogens and to evaluate their impact on proposed vaccine development programs.