Intravenous immune globulin suppresses angiogenesis in mice and humans
Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural
Grantová podpora
R01 EY017182
NEI NIH HHS - United States
R00 EY024336
NEI NIH HHS - United States
R01 EY018350
NEI NIH HHS - United States
K99 EY024336
NEI NIH HHS - United States
UL1 RR033173
NCRR NIH HHS - United States
R01 EY018836
NEI NIH HHS - United States
R01 EY020672
NEI NIH HHS - United States
T32 HL091812
NHLBI NIH HHS - United States
R01 EY024068
NEI NIH HHS - United States
R01 EY017950
NEI NIH HHS - United States
DP1 GM114862
NIGMS NIH HHS - United States
R01 EY022238
NEI NIH HHS - United States
PubMed
26925256
PubMed Central
PMC4768485
DOI
10.1038/sigtrans.2015.2
PII: 15002
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~ 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels.
Angiogenesis Lab Institute of Genetics and Biophysics CNR Naples Italy
Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
Department of Nephrology Institute for Clinical and Experimental Medicine Prague 4 Czech Republic
Department of Ophthalmology and Visual Sciences University of Kentucky Lexington KY USA
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