RESUMO
R-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras(-/-) mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras(-/-) mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras(-/-) DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras-GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras(-/-) DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/genética , Células Dendríticas/fisiologia , Ativação Linfocitária/genética , Proteínas ras/fisiologia , Animais , Apresentação de Antígeno/genética , Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Células Dendríticas/metabolismo , Feminino , Imunidade Celular/genética , Imunidade Celular/imunologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
BACKGROUND: Members of the established public health systems and medical community must understand that, in medical surge events, members of the dental profession and other non-traditional disaster health care personnel are an additional source of assistance in response activities. METHODS: The authors relied on hands-on experience, expert consultations, literature reviews and Web searches to identify disaster response training programs appropriate for members of the dental profession and other health care personnel. RESULTS: The authors identified multiple governmental and professional disaster training programs. CONCLUSIONS: Five key national-level programs address the training and organization of health care professionals to support a large-scale disaster program. Because of their training and skills, dental professionals would be valuable additions to these programs and could make significant contributions if natural disasters and/or terrorist events were to occur.
