Abstract
Background: ICAM-1 and P-selectin are molecules that facilitate adhesion of circulating leukocytes
to vessel walls. We have investigated the role of donor-derived ICAM-1 and P-selectin
in acute and chronic cardiac allograft rejection.
Methods
C57BL/6J (H-2b) mice were used as donors for heterotopic heart transplantation into CBA/Ca (H-2k) recipients. The donors were wild-type or homozygous for gene mutations of ICAM-1
or P-selectin. We measured acute rejection in non-immunosuppressed recipients by daily
palpation and sacrificed mice at Days 2, 4, and 6 for immunohistochemical analysis.
For chronic rejection, recipients received monoclonal antibody against CD4+ T cells.
We removed hearts at Days 60 to 62 for histologic assessment of vasculopathy using
quantitative morphometry to measure intimal thickening.
Results
Time (days) to rejection was 7.1 ± 0.57 for wild-type (n = 10), 7.0 ± 0.71 for ICAM-1 −/− (not significantly different, n = 7) and 6.1 ± 0.33 (p = 0.001) for P-selectin −/− donors. ICAM-1 deficiency was associated with delayed
infiltrate at Day 4 compared with wild-type. In the model of chronic rejection, elastin-positive
vessels showed a mean occlusion of 34% ± 3% in transplanted wild-type hearts; vessels
were divided into those showing 0% to 20%, 20% to 50%, and 50% to 100% occlusion.
We observed no difference in the number of affected vessels or the amount of vascular
thickening in donors lacking ICAM-1 or P-selectin compared with wild-type controls.
Conclusions
The absence of ICAM-1 or P-selectin in donor tissues neither lengthens the time of
allograft survival nor inhibits the vascular lesions associated with chronic rejection.
Indeed, the absence of P-selectin may exacerbate alloimmune injury.
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Article info
Publication history
Accepted:
August 4,
2000
Received:
June 9,
2000
Identification
Copyright
© 2001 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
