Induction of anti-myelin antibodies in EAE and their possible role in demyelination.
Experimental allergic encephalomyelitis is characterized by invasion of lymphocytes and macrophages into the central nervous system resulting in inflammation, edema, and demyelination. Sera from Lewis rats from 7-95 days after immunization with purified guinea pig CNS myelin were examined with respect to their ability to opsonize myelin. This was correlated with the appearance of antibody components and the relative amounts of antibody to myelin basic protein (MBP) and proteolipid protein (PLP). Sera from rats 10-95 days after immunization preincubated with purified myelin induced phagocytosis of myelin by cultured macrophages with the resulting production of cholesterol ester. This opsonization activity as measured by the percentage of cholesterol esterified reached a peak at 26-27 days after immunization but remained significantly elevated up to 95 days post-immunization compared to the activity of serum from the Freund's adjuvant-injected controls. Immunoblots of the sera revealed a gradual increase in antibody activity against myelin components. ELISA assays for MBP and PLP antibody showed a similar pattern. Antibody to galactocerebroside (GC) was not detected by immunostains nor by the ELISA assay. Areas of demyelination were observed histologically by luxol-fast blue stained spinal cords up to 60 days post-immunization. These results indicate that antibodies to myelin protein when given access to myelin through or within the blood brain barrier could initiate or enhance the phagocytic response by peripheral or resident macrophages.
Sadler
R H
RH
Department of Neurology, Stanford University Medical Center, California.
Sommer
M A
MA
Forno
L S
LS
Smith
M E
ME
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D003711:Demyelinating Diseases / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D009185:Myelin Proteins / Q000032:analysis; D009186:Myelin Sheath / Q000276:immunology* / Q000502:physiology; D010587:Phagocytosis; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D009185:Myelin Proteins