RESUMO
Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of ß2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of ß2-integrins-we show that the Gαs-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of Gαs-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of Gαs-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Sono/fisiologia , Adenosina/metabolismo , Adulto , Antígenos CD18/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/virologia , Catecolaminas/metabolismo , Infecções por Citomegalovirus/metabolismo , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Epinefrina/farmacologia , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Ativação Linfocitária , Masculino , Transdução de SinaisRESUMO
The medical advancements made during the wars in Iraq and Afghanistan have resulted in an unprecedented survival rate, yet there is still a significant number of deaths that were potentially survivable. Additionally, the ability to deliver casualties to definitive surgical care within the "golden hour" is diminishing in many areas of conflict. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been implemented successfully in the hospital setting. REBOA may be a possible adjunct for the Role I and point-of-injury (POI) care to provide temporary control of noncompressible torso hemorrhage (NCTH) and junctional hemorrhage. Here the authors advocate for the development of the Role I Resuscitation Team (RT) and a training pathway to meet the challenge of the changing battlefield.