RESUMEN
During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors.
Asunto(s)
Autoantígenos/metabolismo , Queratinocitos/efectos de la radiación , Ribonucleoproteínas , Rayos Ultravioleta , Autoantígenos/genética , Autoantígenos/farmacocinética , Transporte Biológico/fisiología , Transporte Biológico/efectos de la radiación , Membrana Celular/inmunología , Membrana Celular/metabolismo , Membrana Celular/efectos de la radiación , Núcleo Celular/inmunología , Núcleo Celular/metabolismo , Núcleo Celular/efectos de la radiación , Citoplasma/inmunología , Citoplasma/metabolismo , Citoplasma/efectos de la radiación , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Queratinocitos/metabolismo , Queratinocitos/ultraestructura , Biosíntesis de Proteínas/efectos de la radiación , Transcripción Genética/efectos de la radiación , Antígeno SS-BRESUMEN
Sm ribonucleoprotein complex was immunopurified and labelled with 125I. After i.v. injection into normal mice 125I-Sm was cleared with a half life of less than 3 min, mainly to the liver (54% at 15 min). With time there was a progressive reduction in liver uptake (13.3% at 1 h), and this was associated with the appearance of increasing amounts of trichloroacetic acid soluble 125I in serum, suggesting complete Sm catabolism. Injection of 125I-Sm as a preformed immune complex with human anti-Sm antibody was associated with slower antigen removal from the circulation (half life 15 min), more gradual liver uptake (27% at 1 hr), and less degradation products in the serum than after injection of antigen alone. These data suggest that release of 125I-Sm into the circulation is followed by specific organ uptake and antigen degradation. In the form of an immune complex, the rapid removal mechanism is impaired, and antigen persists in the circulation in an undegraded form. Simultaneous production of anti-Sm antibody and Sm antigen release following tissue destruction could lead to amplification of any primed immune response as a result of autoantigen drive in systemic lupus erythematosus.