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Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation
- Source :
- Nature. 539:570-574
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Macrophage-derived insulin-like growth factor enhances the uptake of microvesicles by non-professional phagocytes, such as airway epithelial cells and fibroblasts, thereby dampening tissue inflammation. Our bodies clear billions of cells every day through the actions of both tissue-resident and recruited 'professional' phagocytes such as macrophages, and neighbouring 'non-professional' phagocytes such as epithelial cells or fibroblasts. The relative contributions of each phagocyte type to phagocytosis and tissue homeostasis in general are not well understood. Kodi Ravichandran and colleagues provide evidence for a role of macrophage-derived insulin like growth factor in enhancing the uptake of microvesicles by non-professional phagocytes, such as airway epithelial cells and fibroblasts, thereby dampening tissue inflammation. Professional phagocytes (such as macrophages1) and non-professional phagocytes2,3,4,5,6,7,8 (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis9. 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 known10. 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.
- Subjects :
- Male
0301 basic medicine
Cell signaling
Phagocyte
Phagocytosis
medicine.medical_treatment
Respiratory System
Apoptosis
Inflammation
Cell Communication
Biology
Article
Receptor, IGF Type 1
Mice
03 medical and health sciences
Somatomedins
medicine
Animals
Humans
Tissue homeostasis
Phagocytes
Multidisciplinary
Macrophages
Growth factor
Epithelial Cells
Pneumonia
Allergens
Fibroblasts
Microvesicles
Cell biology
030104 developmental biology
medicine.anatomical_structure
Immunology
Cytokines
Female
medicine.symptom
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 539
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....ebb4476f262a9253d2372d5c040bfd41