Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis.

Blood
Harald F LangerTriantafyllos Chavakis

Abstract

Beyond its role in immunity, complement mediates a wide range of functions in the context of morphogenetic or tissue remodeling processes. Angiogenesis is crucial during tissue remodeling in multiple pathologies; however, the knowledge about the regulation of neovascularization by the complement components is scarce. Here we studied the involvement of complement in pathological angiogenesis. Strikingly, we found that mice deficient in the central complement component C3 displayed increased neovascularization in the model of retinopathy of prematurity (ROP) and in the in vivo Matrigel plug assay. In addition, antibody-mediated blockade of C5, treatment with C5aR antagonist, or C5aR deficiency in mice resulted in enhanced pathological retina angiogenesis. While complement did not directly affect angiogenesis-related endothelial cell functions, we found that macrophages mediated the antiangiogenic activity of complement. In particular, C5a-stimulated macrophages were polarized toward an angiogenesis-inhibitory phenotype, including the up-regulated secretion of the antiangiogenic soluble vascular endothelial growth factor receptor-1. Consistently, macrophage depletion in vivo reversed the increased neovascularization associated wit...Continue Reading

References

Aug 1, 1994·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·J Pérez, E Perentes
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J KildsgaardR A Wetsel
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 26, 2002·Trends in Immunology·Dimitrios Mastellos, John D Lambris
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·John W CrabbJoe G Hollyfield
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ines J LaudesPeter A Ward
Nov 21, 2002·Biochemical Society Transactions·D Morikis, J D Lambris
Jun 5, 2003·Nature Medicine·Peter Carmeliet
Aug 2, 2003·The New England Journal of Medicine·James C YangSteven A Rosenberg
Aug 26, 2003·The American Journal of Pathology·Susanna H WeerthCedric S Raine
Sep 17, 2003·The Journal of Experimental Medicine·Christoph W StreyJohn D Lambris
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Glenda Trujillo, Richard R Kew
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Puran S BoraNalini S Bora
Jan 7, 2005·Journal of Medicinal Chemistry·Buddhadeb MallikJohn D Lambris
Jan 8, 2005·Circulation Research·Stefan FrantzRalph A Kelly
Mar 12, 2005·Science·Albert O EdwardsLindsay A Farrer
Mar 18, 2005·Annual Review of Immunology·Ren-Feng Guo, Peter A Ward
Aug 27, 2005·Blood·Matina EconomopoulouTriantafyllos Chavakis
Dec 3, 2005·Nature Reviews. Immunology·Siamon Gordon, Philip R Taylor
Feb 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Miho NozakiJayakrishna Ambati
May 23, 2006·Nature Medicine·Markus Huber-LangPeter A Ward
Jun 6, 2006·Experimental Eye Research·Olli Arjamaa, Mikko Nikinmaa
Aug 23, 2006·The Journal of Experimental Medicine·Guillermina GirardiJane E Salmon
Aug 29, 2007·Investigative Ophthalmology & Visual Science·Jikui ShenPeter A Campochiaro
Nov 3, 2007·The Journal of Clinical Investigation·Jennifer KellyRajendra S Apte
Dec 18, 2007·Cell·Beth StevensBen A Barres
Feb 26, 2008·Seminars in Immunopathology·Thomas A Ferguson, Rajendra S Apte
Mar 15, 2008·Seminars in Immunopathology·Anthony P Adamis, Adrienne J Berman
Jul 11, 2008·Trends in Cell Biology·Farbod ShojaeiNapoleone Ferrara
Nov 15, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·K Kaarniranta, A Salminen
Jan 16, 2009·Trends in Immunology·A P SjöbergA M Blom
Mar 7, 2009·Investigative Ophthalmology & Visual Science·Bärbel RohrerStephen Tomlinson
Apr 21, 2009·Nature Medicine·Matina EconomopoulouTriantafyllos Chavakis

❮ Previous
Next ❯

Citations

Aug 15, 2013·Nature Communications·Tracy HaynesKatia Del Rio-Tsonis
Oct 17, 2012·Cardiovascular Research·Margreet R de VriesPaul H A Quax
May 20, 2011·Cancer Research·Harald F LangerTriantafyllos Chavakis
Nov 26, 2011·Journal of Innate Immunity·Lorenza FrancescutCordula Stover
Oct 29, 2011·Journal of the American Society of Nephrology : JASN·Sandrine Le RouxFadi Fakhouri
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Fleur BossiFrancesco Tedesco
May 17, 2014·Inflammatory Bowel Diseases·Umang JainAndrew W Stadnyk
Feb 12, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Frédéric LavainneFadi Fakhouri
Sep 26, 2015·Clinical and Experimental Immunology·M A KhanD C Broering
May 25, 2012·Immunobiology·Alexandre FisetteKatherine Cianflone
Jul 10, 2012·Protein & Cell·Karine R Mayilyan
Jan 7, 2016·Frontiers in Microbiology·Chloe R McDonaldKevin C Kain
May 24, 2011·Molecular Immunology·Guillermina GirardiSicco Scherjon
May 10, 2011·Molecular Immunology·Trent M WoodruffFrancesco Tedesco
Aug 2, 2015·Blood·Rebecca I SchleicherHarald F Langer
Aug 28, 2015·Thrombosis and Haemostasis·Matina EconomopoulouTriantafyllos Chavakis
Aug 12, 2014·BioMed Research International·Jiamin ZhouJi Ming Wang
Sep 7, 2013·Thrombosis and Haemostasis·A Verschoor, H F Langer
Mar 1, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Cornelia Volz, Diana Pauly
Sep 17, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Stefan RecknagelAnita Ignatius
Mar 13, 2014·Cell Reports·Min Soon ChoVahid Afshar-Kharghan
Dec 19, 2014·American Journal of Reproductive Immunology : AJRI·Stephanie H GusehRichard M Burwick
May 3, 2014·Neuroscience·L Peruzzotti-JamettiS Pluchino
May 28, 2013·Seminars in Immunology·Ruben PioJohn D Lambris
May 21, 2013·Seminars in Immunology·Julia PhielerTriantafyllos Chavakis
Jul 24, 2015·Science Translational Medicine·J Harry SweigardKip M Connor
Jul 23, 2015·Journal of Biomedical Science·M Afzal KhanD C Broering
Jan 9, 2013·Molecular and Cellular Endocrinology·Waldemar KanczkowskiStefan R Bornstein
May 23, 2013·Seminars in Immunology·Inken SchmuddeJörg Köhl
Aug 21, 2012·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Ratana Lim, Martha Lappas
Nov 27, 2010·Blood·Walter H A Kahr
Apr 26, 2016·American Journal of Reproductive Immunology : AJRI·Paola TriggianeseRoberto Perricone
Dec 3, 2014·Trends in Molecular Medicine·Abdoulaye SeneRajendra S Apte
Nov 3, 2016·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Yingdong HeMinghui Zhao
Jul 30, 2016·Current Opinion in Lipidology·Margreet R de Vries, Paul H A Quax
Oct 28, 2016·European Journal of Medical Research·Christian EhrnthallerAnita Ignatius

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