Perforin mediates endothelial cell death and resultant transplant vascular disease in cardiac allografts.

TitlePerforin mediates endothelial cell death and resultant transplant vascular disease in cardiac allografts.
Publication TypeJournal Article
Year of Publication2004
AuthorsChoy, JC, Kerjner, A, Wong, BW, McManus, BM, Granville, DJ
JournalAm J Pathol
Volume165
Issue1
Pagination127-33
Date Published2004 Jul
ISSN0002-9440
KeywordsAnimals, Apoptosis, Arteries, Coronary Vessels, Endothelium, Vascular, Graft Rejection, Heart Transplantation, Immunohistochemistry, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Perforin, Pore Forming Cytotoxic Proteins, Transplantation, Heterotopic, Transplantation, Homologous, Vascular Diseases
Abstract

T cell-induced endothelial injury is an important event in the development of transplant vascular disease (TVD), the leading expression of chronic rejection of vascularized organ transplants. However, the precise contribution of perforin to vascular damage in allografts and resultant TVD has not been addressed in vivo. Minor histocompatability antigen mismatched mouse heterotopic cardiac transplants were performed from 129J donors into C57Bl/6 (wild-type (WT)) or perforin knockout (PKO) recipients. Perforin was abundant in immune infiltrates in the myocardium and vasculature of transplanted hearts in WT mice. Allograft coronary arteries in both WT and PKO mice had considerable vasculitis. There was also marked endothelial disruption, as well as TUNEL-positivity in the endothelial region, in coronary arteries of hearts transplanted into WT mice that was not evident in PKO recipients (P = 0.05). At 30 days post-transplantation, intimal thickening was assessed on elastic Van Gieson-stained ventricular sections. There was an average of 54.2 +/- 6.7% luminal narrowing of coronary arteries in allografts from WT mice as compared to 13.4 +/- 5.1% luminal narrowing in PKO counterparts (P < 0.00002). In summary, perforin plays a primary role in endothelial damage and the resultant onset and progression of TVD.

DOI10.1016/S0002-9440(10)63281-6
Alternate JournalAm. J. Pathol.
PubMed ID15215168
PubMed Central IDPMC1618552