In vivo modulation of oligodendrocyte function by an anti-receptor antibody.
The receptor for reovirus serotype 3 (Reo3R) is biochemically, pharmacologically, and antigenically related to the adrenergic receptors. Previous studies have demonstrated that anti-Reo3R antibodies and Reo3R-binding peptides alter oligodendrocyte differentiation in culture. In the present studies, antibodies and peptides that bind the Reo3R were found to alter myelin morphology in vivo. Microinjection of purified anti-Reo3R antibody into guinea pig optic nerves produced expansion of the adaxonal oligodendrocyte cytoplasm, separation of myelin lamellae, widening of Schmidt-Lanterman clefts, myelin vesiculation, and demyelination. A divalent Reo3R-binding peptide reproduced some of these changes. Anti-Reo3R antibodies and Reo3R-binding peptides alter oligodendrocyte function in vivo resulting in myelin changes. These effects appear to be mediated directly by Reo3R perturbation, at least in part, rather than through activation of additional effector mechanisms.
Cohen
J A
JA
Department of Neurology, University of Pennsylvania, Philadelphia 19104-4283.
Sergott
R C
RC
Williams
W V
WV
Hill
S J
SJ
Brown
M J
MJ
Greene
M I
MI
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002454:Cell Differentiation; D003711:Demyelinating Diseases; D006168:Guinea Pigs; D012089:Mammalian orthoreovirus 3; D008845:Microinjections; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000276:immunology / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011991:Receptors, Virus / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D010446:Peptide Fragments; D011943:Receptors, Adrenergic, beta; D011991:Receptors, Virus