Role of macrophages in myocardial apoptosis following cardiac
transplant. Influence of immunosuppressive treatment
F. Jurado, J.M. Bellón, A. Golitsin,
M.J. Gimeno, G. Pascual and J. Buján
Department of Morphological Sciences and Surgery
(Surgical Research Laboratory), Faculty of Medicine,
University of Alcalá de Henares, Madrid, Spain
Offprint requests to: Prof.
Julia Buján, PhD., Department of Morphological Sciences
and Surgery, Faculty of Medicine, University of Alcalá
de Henares, Crta. Madrid-Barcelona Km. 33,600, 28871- Alcalá
de Henares (Madrid), Spain. Fax: 34.91885-48-85. e-mail: email@example.com
T cells may induce myocardial apoptosis by histiocyte activation
during rejection following allogenic heart transplant. The aim
of the present investigation was to evaluate the macrophage response
and its relationship to the programmed death of cardiomyocytes
in rejection and during cyclosporin-A (CsA) treatment.
An abdominal, heterotopic heart transplant rat model was used
establishing two groups: singenic (ST) and allogenic (AL) transplant.
5mg/kg/day (s.c.) CsA (Sandimun®) was administered to half
of the animals in each group. Morphological and structural analysis
was performed 7, 14, 21, 30, 50 and 100 days post-transplant.
Macrophages were detected using the monoclonal antibody (ED1).
The TUNEL method was used to visualise apoptotic cells.
Two weeks after ST in animals without immuno-suppressive treatment,
the transplanted myocardium had been extensively infiltrated by
inflammatory cells, many of which were ED1-positive. At 21 days
follow-up, the number of labelled cells had fallen. In animals
treated with CsA the amount of ED1-positive cells was lower than
that seen in the anterior group. Only a few isolated cells of
the infiltrate were TUNEL-positive. In the AT group, rejection
took place between 9-15 days in the untreated animals. The myocardium
was highly infiltrated by mononuclear cells. Some were ED1-positive.
Small groups of apoptotic cells were visible in the infiltrate
and in some vessel lumens. Rejection was resolved in animals treated
with CsA. The macrophage response diminished during follow-up
in a similar way to that occurring in the ST. Few cells showed
TUNEL positivity. It may be concluded that: a) CsA treatment diminishes
the amount of infiltrated macrophages; b) animals receiving ST
or AT, show a low level of apoptosis; c) in the present model,
the apoptosis of cardiomyocytes does not appear to be induced
by macrophages; and d) in this model it is not possible to relate
apoptosis and rejection. Histol. Histopathol. 14, 1033-1043
Key words: Apoptosis,
Macrophages, Allogenic transplant, Acute rejection, Cyclosporin