BACKGROUND: It is now generally accepted that complement activation is critical for the hyperacute rejection of xenografts. Activation of the classical pathway as the result of the interaction of xenoreactive IgM xenoantibodies with the vascular endothelium has been observed in all species combinations examined to date. A number of studies using a variety of species combinations have also implicated alternate pathway involvement; however, these studies do not enable a conclusion to be drawn as to whether the alternate pathway can be activated in the complete absence of classical pathway activation. METHODS: In this study, human plasma was depleted of both Clq and factor D and then reconstituted with purified Clq or factor D to restore the classical and alternate complement pathways, respectively. The ability of these modified plasmas to prosecute hyperacute rejection was then examined using an ex vivo isolated mouse heart perfusion model based on the Langendorff system. RESULTS AND CONCLUSIONS: In the mouse to human species combination, both the classical and alternate pathways of complement are independently capable of initiating complement activation and mediating xenograft rejection.
BACKGROUND: It is now generally accepted that complement activation is critical for the hyperacute rejection of xenografts. Activation of the classical pathway as the result of the interaction of xenoreactive IgM xenoantibodies with the vascular endothelium has been observed in all species combinations examined to date. A number of studies using a variety of species combinations have also implicated alternate pathway involvement; however, these studies do not enable a conclusion to be drawn as to whether the alternate pathway can be activated in the complete absence of classical pathway activation. METHODS: In this study, human plasma was depleted of both Clq and factor D and then reconstituted with purified Clq or factor D to restore the classical and alternate complement pathways, respectively. The ability of these modified plasmas to prosecute hyperacute rejection was then examined using an ex vivo isolated mouse heart perfusion model based on the Langendorff system. RESULTS AND CONCLUSIONS: In the mouse to human species combination, both the classical and alternate pathways of complement are independently capable of initiating complement activation and mediating xenograft rejection.
Authors: Abhijit Jagdale; Huy Nguyen; Juan Li; KaLia Burnette; David Ayares; David K C Cooper; Hidetaka Hara Journal: Int J Surg Date: 2020-09-25 Impact factor: 6.071
Authors: M Mora; M Lazzer; G Marsicano; L C Mulder; L Carraresi; A Pieri; A Benanchi; D Grifoni; S Nuti; P Bruzzone; M Comporti; R Cortesini; M Rossini Journal: Transgenic Res Date: 2000-06 Impact factor: 2.788
Authors: S Le Bas-Bernardet; X Tillou; J Branchereau; N Dilek; N Poirier; M Châtelais; B Charreau; D Minault; J Hervouet; K Renaudin; C Crossan; L Scobie; Y Takeuchi; M Diswall; M E Breimer; N Klar; M R Daha; P Simioni; S C Robson; M B Nottle; E J Salvaris; P J Cowan; A J F d'Apice; D H Sachs; K Yamada; I Lagutina; R Duchi; A Perota; G Lazzari; C Galli; E Cozzi; J-P Soulillou; B Vanhove; G Blancho Journal: Am J Transplant Date: 2015-02 Impact factor: 8.086