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Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation.
- Source :
-
Immunity [Immunity] 2017 Feb 21; Vol. 46 (2), pp. 261-272. - Publication Year :
- 2017
-
Abstract
- Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47. The AMD-associated CFH(H402) variant markedly increased this inhibitory effect on microglial cells, supporting a causal link to disease etiology. This mechanism is not restricted to the eye, as similar results were observed in a model of acute sterile peritonitis. Pharmacological activation of CD47 accelerated resolution of both subretinal and peritoneal inflammation, with implications for the treatment of chronic inflammatory disease.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Complement Factor H genetics
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunohistochemistry
Inflammation genetics
Macular Degeneration genetics
Mice
Mice, Knockout
Peritonitis genetics
Peritonitis immunology
Polymorphism, Single Nucleotide
CD47 Antigen immunology
Complement Factor H immunology
Inflammation immunology
Macular Degeneration immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 46
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 28228282
- Full Text :
- https://doi.org/10.1016/j.immuni.2017.01.006