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03b. Macrofagos
03b. Macrofagos
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Revisin
Inmunologa
Vol. 26 / Nm 2/ Abril-Junio 2007: 73-86
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- and/or TNF- 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.
PALABRAS CLAVE: Activacin del Macrfago/ Complejos Inmunes/ Factor Transformante del Crecimiento/ Glucocorticoides/
Interleucina-4/ Interleucina-10/ Interleucina-13/ Activacin Clsica/ Activacin Alternativa.
KEY WORDS: Macrophage Activation/ Glucocorticoids/ Immune Complexes/ Interleukin-13/ Interleukin-4/ Interleukin-10/
Transforming Growth Factor/ Alternative Activation/ Classical Activation.
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INTRODUCCIN
Los macrfagos son una de las poblaciones celulares
ms pleiotrpicas del sistema inmune, presentes en todos
los tejidos del cuerpo. Tienen funciones homeostticas que
incluyen reparacin, modelacin y angiognesis de los tejidos
y proveen proteccin al poner en marcha mecanismos
inmunes innatos e iniciar el desarrollo de respuestas inmunes
especficas a travs del procesamiento y presentacin
antignicos, la expresin de molculas coestimulatorias y
la produccin de citocinas(1). Debido a su determinante
influencia, el estudio de sus patrones de activacin se ha
convertido en un tpico de gran impacto. Aunque actualmente
se habla de diferentes estados de activacin, entre los que
se encuentran el clsico y el alternativo, no est del todo
claro cules son los inductores, las propiedades funcionales
y el repertorio molecular de cada uno de estos grupos de
macrfagos, ya que las definiciones de los diferentes fenmenos
asociados a la activacin varan entre los sistemas
experimentales. Slo hasta hace poco el papel de la
heterogeneidad y la diferenciacin del macrfago ha sido
tomado en cuenta en la definicin de los diferentes fenotipos
de activacin, con lo cual se ha comenzado a comprender
que los macrfagos activados son un grupo de clulas mucho
ms amplio y verstil, que llevan a cabo distintas funciones,
resultado de un continuum de diferenciacin, maduracin
y activacin.
En esta revisin se pretende examinar algunos aspectos
relevantes acerca de la activacin alternativa del macrfago:
su origen como concepto, las molculas inductoras y las
caractersticas fenotpicas y funcionales que presentan estas
formas de activacin, a fin de describir un panorama actual
de este fenmeno que permita abandonar la sobresimplificacin conceptual que ha comenzado a erosionar
su importancia.
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CONCLUSIN
El vasto repertorio de funciones exhibidas por los
macrfagos M2 y su compleja regulacin, detentan una
avasalladora diversidad. Aunados estos eventos a la
heterogeneidad implcita de los fagocitos mononucleares
y su diferenciacin, se torna el panorama en todo un universo
inexplorado. Entender las bases moleculares que regulan
e inducen los distintos fenotipos M2 y que determinan el
momento en que estas clulas deben aparecer y ejercer su
papel es apenas un primordio que abre nuevas posibilidades
en la comprensin de la patognesis de diferentes
enfermedades y despliega una plyade de posibilidades
en la modulacin de las alteraciones en la regulacin de
la respuesta inflamatoria.
CONFLICTO DE INTERS
Los autores declaran no tener conflicto de inters.
CORRESPONDENCE TO:
Dr. Mauricio Rojas Lpez
Grupo de Inmunologa Celular e Inmunogentica
Facultad de Medicina, Sede de Investigacin Universitaria
Universidad de Antioquia, Cra 53 No. 61-30
Medelln, Colombia
Tel: +57 4 210 6461, Fax: +57 4 210 64 51
E-mail: mrojasl@une.net.co
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