P.D. Milosavljevic*, Marina Milenkovic**, M. Colic*, Miroslava Dimitrijevic**.
*Institute of Medical Research, Military Medical Academy, Belgrade and **Department of Microbiology and Immunology, Faculty of Pharmacy, Belgrade, Yugoslavia
This work was published at the "Second Balkan Immunology Conference" - Varna (Bulgaria) 1-4. October 1998.
Introduction: Autoimmune myocarditis is a disease of unknown ethiology and not well understood pathogenetic mechanisms. An experimental disease model has been developed to induce autoimmune myocarditis in genetically susceptible DA rats with the aim to investigate immunohistological changes in the course of the disease with special reference to the expression of the dendritic cell (DC) and macrophage (MŲ) markers.
Materials and methods: Male DA rats were immunized
with porcine cardiac myosin in complete Freunds adjuvant (CFA). Animals
were sacrificed at the different time points after the disease induction.
Immunopathological changes of the heart tissue and phenotype of infiltrating
cells were examined using immunoperoxidase and immunoalkaline phosphatase
methods and monoclonal antibodies specific for rat MHC class II (OX6),
CD80 and CD86 (costimulatory molecules), OX62 (rat dendritic cells), ED1
(inflammatory MŲ), ED2 and RMC42 (residual MŲ).
Day 17: The most numerous cells in inflammatory
infiltrates were ED1+ macrophages
Results: In the hearts of control animals DC, predominantly localized in the interstitium, were OX6hi CD86lo CD80- OX62-. Residual macrophages ED2+ and subpopulation of RMC42+ MŲ were also present in heart interstitium. ED1+ inflammatory MŲ were rare. In the hearts of diseased animals the first changes were observed after one week, which were manifested as an increase in the expression of MHC class II (OX6) molecules. Rare perivascular DC, phenotypically OX6+ OX62+ CD86+ CD80lo appeared. On day 17, large cell infiltrates were observed. The most numerous cells in them were ED1+ inflammatory MŲ. DC in the infiltrates were also numerous and expressed strongly OX6, OX62 and CD86 markers, whereas the expression of CD80 was still lower. The number of OX62+ DC was lower then the numbers of other cells suggesting that CD80, CD86 as well as MHC class II molecules were also present on other cell types in the infiltrates, probably on macrophages. The number of DC and residual MŲ in the interstitium was not significantly changed. Thirty two days after the disease induction, inflammatory infiltrates were reduced followed by the decrease in the DC and MŲ number but the expression of the examined markers on them was at the same levels as on day 17.
Conclusion: Our immunohistological analysis showed
that ED1+ MŲ and DC constitute a most significant population
of cells in inflammatory infiltrates which probably migrated from circulation
rather than migrated from the heart interstitium.
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