ALLOGRAFT MODELS
Chlamydia Pneumoniae Infection Is Not Associated With Chronic
Transplant Dysfunction in a Rat Aortic Allograft Model
G.T.L. Kloppenburg, H.C. Graeler, G.E.L.M. Grauls, C.A. Bruggeman, and F.R. Stassen
ABSTRACT
Long-term survival of solid-organ transplants is limited as a result of chronic transplant
dysfunction (CTD), which is characterized by occlusion of intragraft vascular tissue due to
myointimal hyperplasia. Recent studies have shown a role for infections in vascular
pathologies. For example, Chlamydia pneumoniae (Cpn) has been shown to aggravate
atherosclerosis, and Cpn immunoglobulin (Ig)G titers correlate with severity of allograft
atherosclerosis after cardiac transplantation. In this study, we evaluated the effect of Cpn
infection on CTD using a rat aortic allograft model. Orthotopic abdominal aorta
transplantations (Tx) were performed with Brown Norway rats as donors and Lewis rats as
recipients. Rats were humanely killed at 1 or 8 weeks after surgery. The graft was
processed for DNA isolation and histological examination. Influx of macrophages and
T cells was assessed using immunohistochemistry. At 1 week after Tx, the perivascular
influx of inflammatory cells in the graft was not affected by Cpn infection. Furthermore,
only limited numbers of Cpn DNA copies were found in the graft at 1 week after Tx. In
addition, Cpn did not alter the severity of myointimal hyperplasia in the rat aortic allograft
model at 8 weeks after surgery. Our data suggested that, in the rat aortic allograft model,
Cpn infection did not influence the influx of inflammatory cells or the severity of CTD.
O
RGAN transplantation has become an increasingly
successful medical treatment for patients with end-
stage organ failure. However, despite improvements in
immunosuppressive drug therapy and treatment of acute
rejection, long-term survival of solid-organ transplants is
limited as a result of chronic transplant dysfunction (CTD).
In the majority of organs, CTD is characterized by a
persistent perivascular inflammation, which results in a
diffuse multifocal myointimal hyperplasia and inadequate
vascular remodeling resulting in intimal narrowing of all the
vessels in the graft.
1
Major risk factors for CTD are
humoral and cellular immune responses, hyperlipidemia,
and viral infections. Regarding the latter, cytomegalovirus
(CMV) in particular has been associated with CTD. Multi-
From the Department of Medical Microbiology and Maastricht
Infection Centre, University Hospital Maastricht, Maastricht, the
Netherlands.
Address reprint requests to F.R. Stassen, Department of Medical
Microbiology and Maastricht Infection Centre, University Hospital
Maastricht, P. Debyelaan 25, P.O. 5800, 6202 AZ Maastricht, the
Netherlands. E-mail: f.stassen@medmic.unimaas.nl
© 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.10.012
Transplantation Proceedings, 39, 261–267 (2007) 261