RESUMO
We report that B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is expressed in the normal human brain at approximately 10% of that in lymphatic tissues (tonsils and adenoids) and is produced by astrocytes. BAFF was regularly detected by enzyme-linked immunosorbent assay in brain tissue lysates and in normal spinal fluid, and in astrocytes by double fluorescence microscopy. Cultured human astrocytes secreted functionally active BAFF after stimulation with interferon-gamma and TNF-alpha via a furin-like protease-dependent pathway. BAFF secretion per cell was manifold higher in activated astrocytes than in monocytes and macrophages. We studied brain lesions with B cell components, and found that in multiple sclerosis plaques, BAFF expression was strongly up-regulated to levels observed in lymphatic tissues. BAFF was localized in astrocytes close to BAFF-R-expressing immune cells. BAFF receptors were strongly expressed in situ in primary central nervous system (CNS) lymphomas. This paper identifies astrocytes as a nonimmune source of BAFF. CNS-produced BAFF may support B cell survival in inflammatory diseases and primary B cell lymphoma.
Assuntos
Astrócitos/metabolismo , Neoplasias do Sistema Nervoso Central/metabolismo , Linfoma/metabolismo , Proteínas de Membrana/metabolismo , Esclerose Múltipla/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator Ativador de Células B , Receptor do Fator Ativador de Células B , Linfócitos B , Encéfalo/metabolismo , Humanos , Proteínas de Membrana/genética , Especificidade de Órgãos , RNA Mensageiro/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/genética , Regulação para CimaRESUMO
In an effort to increase the density of sequence-based markers for the horse genome we generated 9473 BAC end sequences (BESs) from the CHORI-241 BAC library with an average read length of 677 bp. BLASTN searches with the BESs revealed 4036 meaningful hits (E Assuntos
Cromossomos Artificiais Bacterianos/genética
, Cavalos/genética
, Mapeamento de Híbridos Radioativos/métodos
, Animais
, Sequência de Bases
, Primers do DNA/genética
, Biblioteca Gênica
, Marcadores Genéticos
, Genoma Humano
, Humanos
, Especificidade da Espécie