Cell adhesion molecules in adrenal medulla grafts: enhancement of chromaffin cell L1/Ng-CAM expression and reorganization of extracellular matrix following transplantation.

Intracerebral adrenal medulla grafts have been used in human patients as an experimental treatment for Parkinson's disease, based on studies in animal models of this disorder. However, alterations in chromaffin cell properties after transplantation and the factors controlling graft survival are poorly understood. Since cell adhesion molecules (CAMs) are involved in regeneration and development of neural tissue in vivo and in vitro, the present study was undertaken to determine the expression of CAMs in adrenal medulla isografts. Fragments of rat adrenal medulla were implanted into the right lateral ventricle. The majority of grafts survived quite well, for up to 2 months (the longest studied period). The implanted chromaffin cells did not develop extensive processes. The cells retained tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivity, while phenylethanolamine N-methyltransferase (PNMT) expression was decreased. Surviving transplanted chromaffin cells showed enhancement and spreading of surface L1/Ng-CAM expression as compared to normal chromaffin cells in adrenal medulla. The implanted chromaffin cells demonstrated only partial conversion to neuronal phenotypes. These chromaffin cells did not develop extensive processes, but showed an enhancement of L1/Ng-CAM expression. Surviving chromaffin cells were accompanied by reorganization of their closely associated extracellular matrix (ECM). As compared to normal in situ adrenal medulla, graft ECM demonstrated a substantial increase of L1/Ng-CAM and laminin immunoreactivities and a distinct decrease in J1/tenascin expression. Some adrenal medulla grafts degenerated, particularly when misplaced within the host brain parenchyma. In these cases the grafts showed fragmentation of ECM and gradual disappearance of CAMs. These results suggest that surviving adrenal medulla grafts exhibit increased synthesis of certain CAMs by chromaffin cells, which may be involved in interactions between chromaffin cells and the surrounding ECM. It is speculated that both surviving and degenerating adrenal medulla grafts could provide CAMs and ECM components including laminin to host brain and this way contribute to functional effects of grafts.