Involvement of intercellular adhesion molecule-1 in myelin recognition by macrophages

Macrophages play a crucial role in myelin removal during nerve degeneration and demyelination. The exact mechanisms of myelin recognition and uptake a re not yet defined. The present experiments aimed at defining the role of i ntercellular adhesion molecule-1 (ICAM-1) in this process. Myelin phagocyto sis was studied in an established in vitro model of cultured macrophages an d sciatic nerves. Cocultures of wild-type C57BL macrophages with sciatic ne rves resulted in a massive invasion of the nerves by macrophages with subse quent removal of myelin. In contrast, when macrophages of ICAM-1-deficient animals were cocultured with wild-type nerves, myelin phagocytosis was sign ificantly retarded, whereas cell invasion was completely undisturbed. These data indicate that the ICAM-1 molecule acts as a costimulatory signal in m yelin recognition and uptake by macrophages.