Glycolipids and Transmembrane Signaling in Oligodendroglia

Several studies over the last decade have pointed to a role for oligodendroglial glycolipids in cell-cell interactions and signal transduction. Earlier observations by Bornstein and Raine,I. * Fry et u I . , ~ and others implicated antibodies to galactocerebroside as the factor in experimental allergic encephalomyelitis (EAE) and anti-white matter sera responsible for demyelination and destruction of oligodendroglia (OLs) in organ cultures. These effects are complement dependent and apparently due to cell damage and death. Shirazi et u I . ~ more recently showed that antiserum to galactocerebroside causes leukotriene release and sublytic damage in the presence of complement components C5-C9. However, in studies in which complement was absent, several direct effects of antiglycolipid antibodies on myelinogenesis were found. Some of these studies, illustrative of these changes, are summarized in TABLE 1. Diaz et ul. ' reported disorganization of myelinogenesis in organ culture by heat-inactivated anti-white matter serum and showed at the EM level that multiple uncompacted whorls of myelin were seen. Where lamellae could be observed, the major period line appeared to be fused and blurred, suggesting that major structural changes had occurred. In a related study, Lehrer et a/. (' found that synthesis of GalC and sulfatide in organ cultures was stimulated with a similar antiserum; possibly this reflected increased synthesis of glycolipids for the apparent overproduction of membrane or attempts at remyelination. Other groups reported that heat-inactivated anti-white matter or anti-GalC serum inhibited myelination when added to organ cultures at an earlier ~ t a g e . ~ . ~ , ' . ~ Similar effects have been reported for antisera to gangliosides GMI and GM4.9 More recently, Bansal and PfeifferIu showed that a mouse monoclonal antibody against GalC and sulfatide ( R I ~ A B ) " . ~ ~ reversibly blocked OL progenitors at or just beyond the 04+/GalCstage. This same antibody was shown by Ranchst et al.l* to reversibly block myelination of sensory axons by Schwann cells in culture. They showed that GalC was removed from the surface of the Schwann cell and proposed that this prevented interaction with axons, implicating GalC as necessary for axonal contact. An alternate explanation is that the antibody : GalC complex initiated a transmembrane signal that blocked the production and extension of the myelin membrane. Bansal et ~71. '"~'' found that monoclonal antibody 04 (reactive with sulfatide, seminolipid, and an unidentified lipid15.40) stimulates myelinogenesis when cells are grown at high density, perhaps by enhancing aggregation of the cells. However, at lower cell densities, antibody 04 interfered with formation of processes and membrane sheets.ls The interference with process formation at low density may be related to the sheet contraction seen with antiGalC on older oligodendroglia grown at relatively low density. Several in viuo studies have demonstrated the effects of antibodies to glycolipids on oligodendroglia; the roles of complement and other serum factors in these changes are not known. Injection of antibody to GalC directly into sciatic