Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid.
Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked.
Podbielska
Maria
M
Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA, USA.
Dasgupta
Somsankar
S
Levery
Steven B
SB
Tourtellotte
Wallace W
WW
Annuk
Heidi
H
Moran
Anthony P
AP
Hogan
Edward L
EL
D000107:Acetylation; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000166:cytology; D002417:Cattle; D002555:Cerebrospinal Fluid / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D005699:Galactosylceramides / Q000032:analysis / Q000737:chemistry* / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008070:Lipopolysaccharides / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D016858:Mycoplasma fermentans; D009186:Myelin Sheath / Q000737:chemistry*; D051381:Rats; D013110:Sphingosine / Q000737:chemistry
D000906:Antibodies; D005699:Galactosylceramides; D006017:Glycolipids; D008070:Lipopolysaccharides; D013110:Sphingosine