Increased expression of basic fibroblast growth factor during chronic rejection in intestinal transplants is associated with macrophage infiltrates

Long-term survival of intestinal transplants is hampered by chronic rejecti on (CR). Since transplants with CR demonstrate fibrotic changes, the cytoki ne basic fibroblast growth factor (bFGF) may be involved in the tissue remo delling of chronic intestinal rejection. The aim of this study was to inves tigate the bFGF gene and protein expression and distribution in chronically rejecting intestinal allografts. Orthotopic small bowel transplantation wa s performed in the allogeneic DA-to-AS rat combination. Cyclosporin was adm inistered temporarily to prevent acute rejection. Controls were DA isograft s and normal DA. bFGF gene expression was evaluated using reverse transcrip tase polymerase chain reaction (RT-PCR) of the ileum RNA and was standardiz ed against Glyceraldehyde-3-phosphate-dehydrogenase (GBPDH) expression, bFG F protein was determined using immunohistochemistry. To identify the bFGF-p ositive cell type, sequential sections were stained for cell markers. Allog rafts showed histological features of CRI whereas isografts: preserved norm al architecture, bFGF gene expression was present in normal ileum and signi ficantly upregulated in allografts. Immunohistochemical staining showed a s ignificant increase in bFGF protein compared to isografts. Most bFGF-positi ve cells were localized in the submucosa and muscularis, particularly aroun d the ne ural plexus. bFGF-positive cells appeared to be ED-2-positive macr ophages, strongly suggesting that the site of bFGF production is the activa ted macrophage. This study demonstrates increased bFGF mRNA and protein in chronically rejecting intestinal allografts that appear to be produced by m acrophages.