RESUMEN
Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (grB) that protects cytotoxic lymphocytes from grB-mediated death. In addition, Sb9 is also expressed in accessory immune cells, including dendritic cells (DCs), although its role is debated. Recently, we have demonstrated that Sb9 plays a grB-independent role in cross-presentation of antigens by CD8+ DCs. Here, using a mouse line expressing green fluorescent protein knocked in under the control of the Sb9 promoter, we demonstrate that Sb9 expression is highest in those tissue-resident and migratory DC subsets capable of cross-presentation. Further, we show that CD8+ DCs can be divided into two subsets based on Sb9 expression, and that only the subset expressing higher levels of Sb9 is capable of cross-presentation. These findings add support for role for Sb9 cross-presentation, and indicate that high Sb9 expression is a novel marker of cross-presentation capable DCs.
Asunto(s)
Reactividad Cruzada/inmunología , Células Dendríticas/inmunología , Proteínas de la Membrana/inmunología , Serpinas/inmunología , Animales , Femenino , Citometría de Flujo , Técnicas de Sustitución del Gen , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Although proteolysis mediated by granzymes has an important role in the immune response to infection or tumours, unrestrained granzyme activity may damage normal cells. In this review, we discuss the role of serpins within the immune system, as specific regulators of granzymes. The well-characterised human granzyme B-SERPINB9 interaction highlights the cytoprotective function that serpins have in safeguarding lymphocytes from granzymes that may leak from granules. We also discuss some of the pitfalls inherent in using rodent models of granzyme-serpin interactions and the ways in which our understanding of serpins can help resolve some of the current, contentious issues in granzyme biology.
Asunto(s)
Citoprotección/fisiología , Granzimas/metabolismo , Sistema Inmunológico/fisiología , Serpinas/metabolismo , Linfocitos T Citotóxicos/enzimología , Animales , Humanos , Proteínas de la Membrana/metabolismo , Ratones , Serina Endopeptidasas/metabolismo , Serpinas/química , Serpinas/genética , Proteínas Virales/metabolismoRESUMEN
Serine proteases are important components of the immune system, playing a role in many processes including migration, phagocytosis and elimination of virally infected and cancerous cells. Members of the serpin superfamily regulate the activity of these proteases to limit tissue damage and unwarranted cell death. This review focuses on the role of intracellular (clade B) serpins in maintaining viability of both innate and adaptive immune cells.
Asunto(s)
Sistema Inmunológico/enzimología , Sistema Inmunológico/inmunología , Familia de Multigenes , Inhibidores de Serina Proteinasa/fisiología , Serpinas/fisiología , Vertebrados/inmunología , Vertebrados/metabolismo , Animales , Humanos , Sistema Inmunológico/patología , Mediadores de Inflamación/química , Mediadores de Inflamación/clasificación , Mediadores de Inflamación/fisiología , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/clasificación , Inhibidores de Serina Proteinasa/genética , Serpinas/química , Serpinas/clasificación , Serpinas/genética , Vertebrados/genéticaRESUMEN
The authors present angiographic demonstration of bilateral, congenital, total absence of the internal carotid arteries in a patient with subarachnoid hemorrhage. Angiography demonstrated complete absence of both internal carotid arteries. The intracranial blood supply had been provided by communication between a hypertrophied basilar artery and the circle of Willis through the posterior communicating arteries. An aneurysm, believed to be the site of the subarachnoid hemorrhage, arose from the basilar artery. Absence of the carotid canals substantiated the congenital nature of the anomaly. The related embryology is reviewed.