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| 1 | Intravenous immune globulin suppresses angiogenesis in mice and humans显示文摘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. | Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano Nagaraj Kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid E Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek Bradley D Gelfand Ana Bastos-Carvalho Sandro De Falco Jayakrishna Ambati | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 3 |
| 2 | New types of MYST3CBP and CBP-MYST3 fusion transcripts in t (8,16) (p11, p13) a cute myeloid leukemias 显示文摘 | Murati A Adelaide J Quiliehini B | 2007 | Haematologica2007，92，2： | 1 |
| 3 | Effect of glycerol and amylose enrichment on cassava starch film proper ties 显示文摘 | VANESSA D A ADELAIDE B MARIA V E G | 2007 | Journal of Food Engineering2007，78，3： | 1 |
| 4 | Effect of glycerol and amylose enrichment on cassava starch film properties显示文摘 | Vanessa D A Suzana M Adelaide B | 2007 | Journal of Food Engineering2007，78，3： | 1 |
| 5 | Effects of isoflavones on beany flavor and astringency of soymilk and cooked whole soybean grains 显示文摘 | Mercedes C C Adelaide D P B Sandra H P | 1999 | Pesq agropec bras (Brasilia)1999，34，6： | 1 |
| 6 | Human IgG1 antibodies suppress angiogenesis in a target-independent manner显示文摘Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Although bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in mice.Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage migration.Other approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized mice.This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated signaling.Furthermore,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice.Finally,mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis.These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies. | Sasha Bogdanovich Younghee Kim Takeshi Mizutani Reo Yasuma Laura Tudisco Valeria Cicatiello Ana Bastos-Carvalho Nagaraj Kerur Yoshio Hirano Judit Z Baffi Valeria Tarallo Shengjian Li Tetsuhiro Yasuma Parthasarathy Arpitha Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Menotti Ruvo Annamaria Sandomenico Miho Nozaki Ryo Ijima Hiroki Kaneko Yuichiro Ogura Hiroko Terasaki Balamurali K Ambati Jeanette HW Leusen Wallace Y Langdon Michael R Clark Kathryn L Armour Pierre Bruhns J Sjef Verbeek Bradley D Gelfand Sandro De Falco Jayakrishna Ambati | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 0 |
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