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Granzyme B Induces Endothelial Cell Apoptosis and Contributes to the Development of Transplant Vascular Disease
Author(s) -
Choy Jonathan C.,
Cruz Rani P.,
Kerjner Alexandra,
Geisbrecht Jennette,
Sawchuk Tracy,
Fraser Stephanie A.,
Hudig Dorothy,
Bleackley R. Chris,
Jirik Frank R.,
McManus Bruce M.,
Granville David J.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00710.x
Subject(s) - granzyme b , medicine , granzyme , apoptosis , cytotoxic t cell , immunology , immune system , transplantation , perforin , cancer research , pathology , t cell , biology , cd8 , biochemistry , in vitro
Endothelial cell death induced by cytotoxic T cells is a key initiating event in the development of transplant vascular disease (TVD), the leading cause of late solid organ transplant failure. We studied the role of the granzyme B (GrB) pathwaye, which is one of the main mechanisms by which T cells induce apoptosis of allogeneic targets, in the pathogenesis of TVD. Granzyme B, in combination with perforin (pfn), induced apoptosis of cultured endothelial cells. In hearts transplanted into GrB knockout (GrB‐KO) mice, there was a similar level of vasculitis as compared to WT mice, indicating that GrB does not affect immune infiltration into allograft arteries. However, there was a significant reduction in luminal narrowing of allograft arteries from GrB‐KO mice as compared to WT recipients. These results indicate that GrB plays a role in endothelial cell death in allograft arteries and in the resultant development of TVD.