Experimental transplantationAnti-proliferative properties of the phosphodiesterase-4 inhibitor rolipram can supplement immunosuppressive effects of cyclosporine for treatment of obliterative bronchiolitis in heterotopic rat allografts
Section snippets
Rats
Allogeneic and syngeneic transplantations were performed from Brown-Norway (BN) to Lewis (Lew) and from Lewis to Lewis strains of rats, respectively. Inbred BN (BN/Crl BR) and Lew (LEW/Crl BR) animals were purchased from Charles River (Sulzfeld, Germany). All animals were male, 7 to 10 weeks of age, and weighed 200 to 230 g. The rats were allowed free access to standard-pellet food and water. The rats received humane care in compliance with the Principles of Laboratory Animal Care and the Guide
Epithelium damage
One day after transplantation the respiratory epithelium was diminished in all groups, most probably caused by ischemia during and after transplantation (Figure 1). Thereafter, the coverage of the inner luminal surface layer was re-epithelized from Days 1 to 5. In non-immunosuppressed and rolipram-treated animals the integrity of the epithelial cell layer disappeared, starting on Day 5 FIGURE 1, FIGURE 2. First, the cell surface marker, CD44v6, normally expressed as membranous and luminal
Discussion
The purpose of this study was to compare the effects of CsA and the PDE-4 inhibitor, rolipram, on epithelium disturbance, leukocyte infiltration and proliferation—events suggested to be key steps in the sequential development of OB.
In untreated allografts typical rejection events occurred. The stepwise disturbance of the epithelium started with a lymphocyte-initiated loss of the epithelial cell-cell contacts, followed by a complete predominantly monocyte/macrophage-mediated disturbance until
Acknowledgements
The authors thank B. Jahnke, R. Hentschel and B. Nietsche for excellent technical assistance. We also thank Prof Szelenyi, Dr Marx and Dr Poppe (Arzneimittelwerk Dresden, Asta Medica) for their support in performing the animal studies and for providing rolipram. In addition, we are grateful to Dr H. Fehrenbach for helpful suggestions regarding the digital quantification of immunohistochemical data. This study was supported by Sächsische Aufbaubank.
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