Porcine cytomegalovirus and coagulopathy in pig-to-primate xenotransplantation1
Porcine cytomegalovirus and coagulopathy in pig-to-primate xenotransplantation1
复制标题
猪巨细胞病毒和猪灵长类异种移植中的凝血病1
作者：
B. Gollackner;N. Mueller;S. Houser;I. Qawi;Daniel Soizic;C. Knosalla;L. Buhler;F. Dor;M. Awwad;D. Sachs;D. Cooper;S. Robson;J. Fishman
Background. A rapidly progressive disorder termed consumptive coagulopathy (CC) has been observed frequently in pig-to-baboon renal xenotransplantation. CC may be initiated by endothelial activation and induction of procoagulant factors after immunologic injury or infection, or by molecular incompatibilities between porcine coagulation proteins and primate clotting factors. The activation of porcine (P) cytomegalovirus (PCMV) and baboon (B) CMV infections has been documented in pig-to-primate xenotransplantation. The purpose of this study was to determine the contribution of PCMV and BCMV to CC. Methods. Endothelial activation was assessed by means of measurement of porcine tissue factor (pTF) in a functional assay in primary porcine aortic endothelial cells (PAEC) in vitro. Renal xenografts and native kidneys were studied by immunohistochemistry in immunosuppressed swine and baboons. BCMV and PCMV DNA was measured by quantitative molecular assays using real-time polymerase chain reaction. Results. In vitro, infection of PAEC with PCMV resulted in a significant increase of pTF expression. In vivo, pTF increase occurred without the activation of PCMV in two xenografts, and in four grafts no pTF was detected despite PCMV activation. All animals with graft pTF increase developed CC. BCMV activation in the baboon xenograft recipients did not correlate with CC or pTF increase. Control pigs and baboons had activation of PCMV and BCMV, respectively, but without coagulation abnormalities. Conclusions. PCMV induces endothelial cell activation in vitro with procoagulant expression. However, in vivo, CC and pTF induction has an uncertain relationship to increased replication of PCMV within a xenograft. Although the data do not exclude a contributory role of PCMV in CC, other mechanisms are also likely to contribute to coagulopathies observed in pig-to-primate xenotransplantation.
通过结合地高辛标记的因子 VIIa 和 X，对人动脉粥样硬化斑块中的组织因子进行原位定位。
DOI：
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发表时间：
1996
期刊：
Laboratory investigation; a journal of technical methods and pathology.
影响因子：
--
作者：
Thiruvikraman,SV;Guha,A;Roboz,J;Taubman,MB;Nemerson,Y;Fallon,JT
通讯作者：
Fallon,JT
影响因子：
6.2
作者：
Kozlowski, T;Shimizu, A;Sachs, DH
通讯作者：
Sachs, DH