Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation.
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.
The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22903, USA.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
Claudia Z
CZ
Han
The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22903, USA.
Ignacio J
IJ
Juncadella
The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22903, USA.
Jason M
JM
Kinchen
The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22903, USA.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
Monica W
MW
Buckley
Department of Medicine, University of Virginia, Charlottesville, Virginia 22903, USA.|Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22903, USA.
Alexander L
AL
Klibanov
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22903, USA.
Kelly
K
Dryden
Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, Virginia 22903, USA.|Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22903, USA.
Suna
S
Onengut-Gumuscu
Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia 22903, USA.
Uta
U
Erdbrügger
Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia 22903, USA.
Stephen D
SD
Turner
Department of Medicine, University of Virginia, Charlottesville, Virginia 22903, USA.
Yun M
YM
Shim
Department of Medicine, University of Virginia, Charlottesville, Virginia 22903, USA.|Department of Pathology, University of Virginia, Charlottesville, Virginia 22903, USA.
Kenneth S
KS
Tung
The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22903, USA.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22903, USA.
Kodi S
KS
Ravichandran
D000485:Allergens / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D010586:Phagocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology; D013002:Somatomedins / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D013002:Somatomedins; D017526:Receptor, IGF Type 1