| First Author | Tang J | Year | 2018 |
| Journal | Mol Cell Biol | PubMed ID | 29891514 |
| Mgi Jnum | J:265279 | Mgi Id | MGI:6199250 |
| Doi | 10.1128/MCB.00103-18 | Citation | Tang J, et al. (2018) Neutrophil and macrophage cell surface CSF-1 shed by ADAM17 drives mouse macrophage proliferation in acute and chronic inflammation. Mol Cell Biol |
| abstractText | Macrophages are prominent cells in acute and chronic inflammatory diseases. Recent studies highlight a role for macrophage proliferation post monocyte recruitment in inflammatory conditions. Using an acute peritonitis model, we identify a significant defect in macrophage proliferation in mice lacking leukocyte transmembrane protease ADAM17. The defect is associated with decreased levels of macrophage colony-stimulating factor-1 (CSF-1) in the peritoneum, and is rescued by intraperitoneal injection of CSF-1. Cell surface CSF-1 (csCSF-1) is one of the substrates of ADAM17. We demonstrate that both neutrophils and macrophages are major sources of csCSF-1. Furthermore, acute shedding of csCSF-1 following neutrophil extravasation is associated with elevated expression of iRhom2, a member of the rhomboid-like superfamily, which promotes ADAM17 maturation and trafficking to the neutrophil surface. Accordingly, deletion of hematopoietic iRhom2 is sufficient to prevent csCSF-1 release from neutrophils and macrophages, and to prevent macrophage proliferation. In acute inflammation, csCSF-1 release and macrophage proliferation are self-limiting due to transient leukocyte recruitment and temporally restricted csCSF-1 expression. In chronic inflammation such as atherosclerosis, the ADAM17-mediated lesional macrophage proliferative response is prolonged. Our results demonstrate a novel mechanism whereby ADAM17 promotes macrophage proliferation in states of acute and chronic inflammation. |
