Cerebroside sulfuric ester (sulfatide) induces oxygen radical generation in guinea-pig leukocytes

Previous studies on experimental allergic encephalomyelitis have shown that a number of leukocytes appear in demyelinating lesions of guinea-pig brain. The present studies showed that cerebroside sulfuric ester (sulfatide), a typical component of myelin membranes, stimulated the oxidative metabolism of guinea-pig neutrophils and macrophages, leading to marked generation of oxygen radicals and light emission. Formation of a spin adduct of 5,5-dimethyl-1-pyrroline N-oxide by leukocytes was dependent on the concentration of sulfatide, and correlated well with the generation of superoxide anion and the intensity of chemiluminescence measured in the absence of luminol. The addition of myelin membranes to the sulfatide-stimulated neutrophils amplified the light emission, suggesting an interaction between myelin membranes and those of leukocytes. Assay of the thiobarbituric acid reaction in the mixture of membranes and cells showed that sulfatide-stimulated cells induced lipid peroxidation in myelin membranes. These results suggest that sulfatide released from demyelinating lesions stimulates leukocytes to release toxic oxygen radicals, which attack myelin membranes, leading to a chain reaction of demyelination.