Modulation of Macrophage Efferocytosis in Inflammation
A critical function of macrophages within the inflammatory milieu is the removal of dying cells by a specialized phagocytic process called efferocytosis (to carry to the grave). Through specific receptor engagement and induction of downstream signaling, efferocytosing macrophages promote resolution...
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2011-11-01
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doaj-330bedecd33f4dcb97162314e3f6861c2020-11-24T21:56:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-11-01210.3389/fimmu.2011.0005712942Modulation of Macrophage Efferocytosis in InflammationDarlynn R Korns0S. Courtney Frasch1Ruby eFernandez-Boyanapalli2Peter M Henson3Donna L Bratton4National Jewish Health and Univ of Colorado DenverNational Jewish HealthNational Jewish HealthNational Jewish Health and Univ of Colorado DenverNational Jewish Health and Univ of Colorado DenverA critical function of macrophages within the inflammatory milieu is the removal of dying cells by a specialized phagocytic process called efferocytosis (to carry to the grave). Through specific receptor engagement and induction of downstream signaling, efferocytosing macrophages promote resolution of inflammation by i) efficiently engulfing dying cells, thus avoiding cellular disruption and release of inflammatory contents, and ii) producing anti-inflammatory mediators such as IL-10 and TGF-β that dampen pro-inflammatory responses. Evidence suggests that plasticity in macrophage programming, in response to changing environmental cues, modulates efferocytic capability. Essential to programming for enhanced efferocytosis is activation of the nuclear receptors PPARγ, PPARδ, LXR and possibly RXRα. Additionally, a number of signals in the inflammatory milieu, including those from dying cells themselves, can influence efferocytic efficacy either by acting as immediate inhibitors/enhancers or by altering macrophage programming for longer-term effects. Importantly, sustained inflammatory programming of macrophages can lead to defective apoptotic cell clearance and is associated with development of autoimmunity and other chronic inflammatory disorders. This review summarizes the current knowledge of the multiple factors that modulate macrophage efferocytic ability and highlights emerging therapeutic targets with significant potential for limiting chronic inflammation.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00057/fullInflammationmacrophageEfferocytosisAlternative activationapoptotic cellclassical activation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Darlynn R Korns S. Courtney Frasch Ruby eFernandez-Boyanapalli Peter M Henson Donna L Bratton |
spellingShingle |
Darlynn R Korns S. Courtney Frasch Ruby eFernandez-Boyanapalli Peter M Henson Donna L Bratton Modulation of Macrophage Efferocytosis in Inflammation Frontiers in Immunology Inflammation macrophage Efferocytosis Alternative activation apoptotic cell classical activation |
author_facet |
Darlynn R Korns S. Courtney Frasch Ruby eFernandez-Boyanapalli Peter M Henson Donna L Bratton |
author_sort |
Darlynn R Korns |
title |
Modulation of Macrophage Efferocytosis in Inflammation |
title_short |
Modulation of Macrophage Efferocytosis in Inflammation |
title_full |
Modulation of Macrophage Efferocytosis in Inflammation |
title_fullStr |
Modulation of Macrophage Efferocytosis in Inflammation |
title_full_unstemmed |
Modulation of Macrophage Efferocytosis in Inflammation |
title_sort |
modulation of macrophage efferocytosis in inflammation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2011-11-01 |
description |
A critical function of macrophages within the inflammatory milieu is the removal of dying cells by a specialized phagocytic process called efferocytosis (to carry to the grave). Through specific receptor engagement and induction of downstream signaling, efferocytosing macrophages promote resolution of inflammation by i) efficiently engulfing dying cells, thus avoiding cellular disruption and release of inflammatory contents, and ii) producing anti-inflammatory mediators such as IL-10 and TGF-β that dampen pro-inflammatory responses. Evidence suggests that plasticity in macrophage programming, in response to changing environmental cues, modulates efferocytic capability. Essential to programming for enhanced efferocytosis is activation of the nuclear receptors PPARγ, PPARδ, LXR and possibly RXRα. Additionally, a number of signals in the inflammatory milieu, including those from dying cells themselves, can influence efferocytic efficacy either by acting as immediate inhibitors/enhancers or by altering macrophage programming for longer-term effects. Importantly, sustained inflammatory programming of macrophages can lead to defective apoptotic cell clearance and is associated with development of autoimmunity and other chronic inflammatory disorders. This review summarizes the current knowledge of the multiple factors that modulate macrophage efferocytic ability and highlights emerging therapeutic targets with significant potential for limiting chronic inflammation. |
topic |
Inflammation macrophage Efferocytosis Alternative activation apoptotic cell classical activation |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00057/full |
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