TY - JOUR
T1 - Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation
AU - Han, Claudia Z.
AU - Juncadella, Ignacio J.
AU - Kinchen, Jason M.
AU - Buckley, Monica W.
AU - Klibanov, Alexander L.
AU - Dryden, Kelly
AU - Onengut-Gumuscu, Suna
AU - Erdbrügger, Uta
AU - Turner, Stephen D.
AU - Shim, Yun M.
AU - Tung, Kenneth S.
AU - Ravichandran, Kodi S.
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2016/11/24
Y1 - 2016/11/24
N2 - Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1- and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.
AB - Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1- and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85016163709&partnerID=8YFLogxK
U2 - 10.1038/nature20141
DO - 10.1038/nature20141
M3 - Article
C2 - 27820945
AN - SCOPUS:85016163709
SN - 0028-0836
VL - 539
SP - 570
EP - 574
JO - Nature
JF - Nature
IS - 7630
ER -