Inhibition of complement component C5 prevents clotting in an ex vivo model of xenogeneic activation of coagulation

Xenotransplantation
Dennis RatajA Tiede

Abstract

Xenogeneic thrombotic microangiopathy (TMA) and acute vascular rejection (AVR) prevent long-term survival of porcine xenografts after transplantation into non-human primates. Preformed xenoreactive natural antibodies (XNA) cause endothelial damage and activate the complement system. Mechanisms of xenogeneic coagulation and platelet activation are only poorly characterized. A microfluidic flow chamber was used to study platelet activation and thrombus formation of human platelet-rich plasma (PRP) upon perfusion over wild-type (WT) or α-1,3- galactosyltransferase knockout (GTKO) and human CD46 (hCD46) transgenic porcine aortic endothelial cells (PAEC). Activation of plasma coagulation (thrombin-anti-thrombin complex; TAT) and complement (C3a, C5a) was studied in human platelet-free plasma (PFP) after co-incubation with PAEC. The activation of PAEC (E-Selectin, tissue factor, ICAM-1, ICAM-2, VCAM-1) was studied after incubation with human serum. Eculizumab (200 μg/ml) was used to inhibit terminal complement activation in all experiments. WT-PAEC perfused with human PRP showed thrombus formation at different shear rates (3 dyn/cm(2) : 23 ± 10%; 10 dyn/cm(2) : 17 ± 10% of flow chamber viewing field). GTKO/hCD46 PAEC exhibited reduce...Continue Reading

References

Nov 1, 1991·European Journal of Immunology·J L PlattF H Bach
Mar 1, 1989·Clinical Immunology and Immunopathology·J J HouleS I Rosenfeld
Jul 14, 1999·Molecular Immunology·F TedescoM R Daha
Mar 5, 2002·Nature Biotechnology·Yifan DaiDavid L Ayares
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anand GhanekarDavid R Grant
Mar 23, 2005·The Journal of Experimental Medicine·Ian Del CondeVahid Afshar-Kharghan
May 23, 2006·Nature Medicine·Markus Huber-LangPeter A Ward
Jun 16, 2007·Nature Reviews. Immunology·Yong-Guang Yang, Megan Sykes
May 1, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J C RousselP J Cowan
Jan 21, 2009·Immunology and Cell Biology·Peter J Cowan, Anthony Jf d'Apice
Jan 1, 2010·Xenotransplantation·Björn PetersenHeiner Niemann
Feb 6, 2010·Immunologic Research·Barbara A Wasowska
Jul 18, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Thomas BarbourPeter Hughes
Oct 3, 2012·Nature Reviews. Nephrology·Julien ZuberUNKNOWN French Study Group for aHUS/C3G
Apr 24, 2013·Blood·Anita HillPeter Hillmen
Mar 27, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·H E AhrensH Niemann

❮ Previous
Next ❯

Citations

May 31, 2016·Xenotransplantation·Christopher Burlak
Oct 27, 2016·Immunological Reviews·Lubka T RoumeninaVeronique Fremeaux-Bacchi
Oct 12, 2017·Blood·Daniëlle M CoenenJudith M E M Cosemans
Jan 1, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Wolf RamackersAndreas Tiede
Jan 12, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Wolf RamackersAndreas Tiede
Jun 24, 2020·Heart Failure Reviews·Songren ShuJiangping Song

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Coagulation Signaling Pathways

Coagulation is the process by which a blood clot is formed. This process includes both the formation of a platelet plug as well as a cascade of clotting factors resulting in the formation of fibrin strands. Find the latest research on coagulation signaling pathways here.

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.