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Nature ; 411(6834): 207-11, 2001 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-11346799

RESUMO

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.


Assuntos
Apoptose , Macrófagos Peritoneais/imunologia , Fagocitose , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases , Timo/citologia , Animais , Anticorpos Antinucleares/imunologia , Apoptose/efeitos dos fármacos , Transplante de Medula Óssea , Adesão Celular , Células Cultivadas , Cruzamentos Genéticos , Citocalasina B/farmacologia , Dexametasona/farmacologia , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Listeria monocytogenes/imunologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Microscopia Eletrônica de Varredura , Microesferas , Mutação/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Quimera por Radiação/imunologia , Receptores Fc/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Timo/ultraestrutura , c-Mer Tirosina Quinase
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