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Resumen
Los macrófagos son una de las poblaciones celulares más pleiotrópicas del sistema inmune. Ellos son efectores de la respuesta innata y están involucrados en el inicio y la regulación de las respuestas adaptativas. Esta revisión describe cómo la definición seminal de la activación del macrófago (AM) evolucionó hasta el desarrollo de un modelo de dos clases de macrófagos activados. Los macrófagos activados clásicamente (M1) inducidos por IFN-γ y/o TNF-α muestran un fenotipo tipo Th1, son efectores proinflamatorios y tienen funciones bactericidas, mientras que los macrófagos activados alternativamente (M2), que incluye por lo menos tres fenotipos diferentes solapados (M2a, b, c), exhiben un fenotipo tipo Th2 y están involucrados en la resolución de la inflamación y la curación del tejido. Aunque este modelo clasifica los fenotipos de activación observados, es importante considerar que subestima la complejidad in vivo, donde existe una alta diversidad de estados de macrófagos activados que emergen en respuesta a diferentes estímulos y ambientes, son influenciados por su heterogeneidad y conforman un continuum de activación.
Profundizando acerca de los mecanismos que definen estos fenotipos, será posible entender mejor la influencia y el papel de los macrófagos activados alternativamente en las respuestas inmunes reguladas por ellos y en la patogénesis de diferentes enfermedades asociadas con el desarrollo de este grupo de macrófagos.
Palabras clave:
Activación del Macrófago
Complejos Inmunes
Factor Transformante del Crecimiento
Glucocorticoides
Interleucina-4
Interleucina-10
Interleucina-13
Activación Clásica
Activación Alternativa
Abstract
Macrophages are one of the most pleiotropic cell populations of the immune system. They are effectors of the innate response and are involved in the initiation and regulation of the adaptative responses. This review depicts how the seminal definition of macrophage activation evolved until the development of a model of two major classes of activated macrophages. Classically activated macrophages (M1) induced by IFN-γ and/or TNF-α show a Th1-like phenotype, are pro-inflammatory effectors and have bactericidal functions, while alternatively activated macrophages (M2), that include at least three different overlapping phenotypes, (M2a, b and c), are generated by different mediators, exhibit a Th2-like phenotype and are involved in the resolution of inflammation and wound healing. Although this model classifies the observed phenotypes of activation, it is important to keep in mind that it underestimates the complexity of the situation in vivo, where a high diversity of macrophage activated stages, emerging in response to different stimulus and environments, are influenced by this heterogeneity and conform an activation continuum.
Getting insights about the mechanisms that might define those phenotypes, it will be possible to better understand the influence and role of alternatively activated macrophages in the immune responses regulated by them and in the pathogenesis of different diseases associated with the development of this group of macrophages.
Key words:
Macrophage Activation
Glucocorticoids
Immune Complexes
Interleukin-13
Interleukin-4
Interleukin-10
Transforming Growth Factor
Alternative Activation
Classical Activation
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