HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation.

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.
AuthorsBertrand Calippe, Sebastien Augustin, Fanny Beguier, Hugo Charles-Messance, Lucie Poupel, Jean-Baptiste Conart, Shulong J Hu, Sophie Lavalette, Alexandre Fauvet, Julie Rayes, Olivier Levy, William Raoul, Catherine Fitting, Thomas Denèfle, Matthew C Pickering, Claire Harris, Sylvie Jorieux, Patrick M Sullivan, José-Alain Sahel, Philippe Karoyan, Przemyslaw Sapieha, Xavier Guillonneau, Emmanuel L Gautier, Florian Sennlaub
JournalImmunity (Immunity) Vol. 46 Issue 2 Pg. 261-272 (02 21 2017) ISSN: 1097-4180 [Electronic] United States
PMID28228282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • CD47 Antigen
  • Complement Factor H
Topics
  • Animals
  • CD47 Antigen (immunology)
  • Complement Factor H (genetics, immunology)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation (genetics, immunology)
  • Macular Degeneration (genetics, immunology)
  • Mice
  • Mice, Knockout
  • Peritonitis (genetics, immunology)
  • Polymorphism, Single Nucleotide

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: