Summary
It is postulated that multiple sclerosis might be an autoimmune demyelinating disease of the central nervous system (CNS). The mechanisms involved are unknown but, since the blood-brain barrier (BBB) is damaged, injury to endothelial cells is likely to have occurred. Our previous studies have led us to investigate the autoimmune effect of injuring the blood-brain barrier by immunizing rhesus monkeys with an endothelial cell membrane from the same kind of animals. The immunized animals developed a chronic or a relapsing neurological illness. Histological and ultrastructural examinations of the brain in the acute stage showed infiltrates of mononuclear cells around the blood vessels of the white matter of cerebrum, cerebellum, pons and midbrain, while in the chronic phase, large areas of demyelination and remyelination, especially in the white matter regions, were present. The animals immunized with extraneural antigen, an endothelial cell membrane obtained from human umbilical cord, developed no neurological illness. This results indicate that the brain endothelial cell membrane has an inflammatory encephalitogenic activity which could produce widespread demyelination in animals. The animal model described here may prove to be useful in the pathogenetic investigation of human autoimmune demyelinating diseases.
Similar content being viewed by others
References
Alvord EC Jr, Driscoll BF, Kies MW (1985) Large subpial plaques of demyelination in a new form of chronic experimental allergic encephalomyelitis in the guinea pig. J Neurochem Pathol 3:195–214
Baldwin WM III (1982) The symbiosis of immunocompetent and endothelial cells. Immunol Today 3:267–269
Behan PO (1986) Multiple sclerosis. In: Triger DR (ed) Advanced Medicine, vol 22. Balliere Tindall, London Philadelphia Toronto, pp 365–370
Broman T (1964) Blood-brain barrier damage in multiple sclerosis. Supra-vital test observations. Acta Neurol Scand [Suppl 10] 40:21–24
Brown WJ (1978) The capillaries in acute and subacute multiple sclerosis — a morphometric analysis. Neurology 28:84–92
Chien JL, Li SC, Laine RA, Li YT (1978) Characterization of gangliosides from bovine erythrocyte membranes. J Biol Chem 253:4031–4035
Cohen O, Sela B, Schwartz M, Eshhar N, Cohen IR (1981) Multiple sclerosis-like disease induced in rabbits by immunization with brain gangliosides. Isr J Med Sci 17:711–714
Hart MN, DeBaut LE, Dadewasser KL, Cancilla PA, Henriquez EM (1981) Morphologic effects of antibody to mouse brain endothelium in vivo. J Neuropathol Exp Neurol 40:84–91
Jaffe EA (1973) Culture of human endothelial cells derived from umbilical cord. J Clin Invest 52:2745–2756
Joo F (1986) New aspects to the function of the cerebral endothelium. Nature 321:197–198
Kristensson K, Wiśniewski HM (1977) Chronic relapsing experimental allergic encephalomyelitis. Studies in vascular permeability changes. Acta Neuropathol (Berl) 39:189–194
Kristensson K, Wiśniewski HM, Bornstein MB (1976) About demyelinating properties of humoral antibodies in experimental allergic encephalomyelitis. In vivo and in vitro studies. Acta Neuropathol (Berl) 36:307–314
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Lassmann H, Wiśniewski HM (1979) Chronic relapsing experimental allergic encephalomyelitis. Clinicopathological comparison with multiple sclerosis. Arch Neurol 36:490–497
Lassmann H, Wiśniewski HM (1981) Histogenesis of demyelinating lesions in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis. J Neurol Sci 50:109–121
Lyons MJ, Amador R, Petito C, Nagashima K, Weinreb H, Zabriskie JB (1986) Inhibition of acute experimental allergic encephalomyelitis in mice by colchicine. J Exp Med 164:1803–1808
Mackay IR, Carnegie PR, Coates AS (1973) Immunopathological comparisons between experimental autoimmune encephalomyelitis and multiple sclerosis. Clin Exp Immunol 15:471–482
Madrid RE, Wiśniewski HM, Iqbal K, Pullarkat PK, Lassmann H (1981) Relapsing experimental allergic encephalomyelitis induced with isolated myelin and with myelin basic protein plus myelin lipids. J Neurol Sci 50:399–411
McCarron RM, Kempski O, Spatz M, McFarlin DE (1985) Presentation of myelin basic protein by murine cerebral vascular endothelial cells. J Immunol 134:3100–3103
McMillan SA, Haire M, Middleton D (1980) Antibodies to lymphocytes and smooth muscle in the sera of patients with multiple sclerosis. Clin Immunol Immunopathol 16:374–385
Mrsulja BB, Mrsulja BT, Fujimoto T, Klazo I, Spatz M (1976) Isolation of brain capillaries. A simplified technique. Brain Res 110:361–365
Oppenheimer DR (1976) Demyelinating disease. In: Blackword W, Corsellis JAS (ed) Greenfield neuropathology. Arnold Edward, London, pp 470–499
Paterson PY (1977) Autoimmune neurologic disease. Experimental animal system and implications for multiple sclerosis. In: Talal N (ed) Autoimmunity, genetics, immunologic, virologic and clinical aspects. Academic Press, New York, pp 633–692
Poser CM, Behan PO (1982) Late onset of Guillain-Barré syndrome. J Neuroimmunol 3:27–41
Prineas JW (1985) Demyelinating disease. Handb Clin Neurol 3:213–257
Putnam TJ (1937) Evidences of vascular occlusion in multiple sclerosis. Arch Neurol Psychiatry 37:1298–1321
Raine CS, Stone SH (1977) Animal model for multiple sclerosis. Chronic experimental allergic encephalomyelitis in inbred pigs. NY State J Med 77:1693–1696
Richert JR, Kies M, Alvord EC Jr (1981) Enhanced transfer of experimental allergic encephalomyelitis with Lewis rat lymph node cells. J Neuroimmunol 1:195–203
Schimmel SD, Kent C, Bischoff R, Vagelos PR (1973) Plasma membranes from cultured muscle cells. Isolation procedure and separation of putative plasma-membrane marker enzymes. Proc Natl Acad Sci USA 70:3195–3199
Spatz M, Bembry J, Dodson RF, Hervonen H, Murray MR (1980) Endothelial cell cultures derived from isolated cerebral macrovessels. Brain Res 191:577–582
Tanaka Y, Tsukada N, Koh Ch-S, Yanagisawa N (1987) Anti-endothelial cell antibodies and circulating immune complexes in the sera of patients with multiple sclerosis. J Neuroimmunol 17:49–59
Traugott U, Scheinberg LC, Raine CS (1985) On the presence of Ia-positive endothelial cells and astrocytes in multiple sclerosis lesions and its relevance to antigen presentation. J Neuroimmunol 8:1–14
Tsukada N, Ahmed SA, Behan WMH, Behan PO (1986) Similarities between the Forssman carotid syndrome and experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 69:234–243
Tsukada N, Koh Ch-S, Yanagisawa N, Okano A, Behan WMH, Behan PO (1987) A new model for multiple sclerosis. Chronic experimental allergic encephalomyelitis induced by immunization with cerebral endothelial cell membrane. Acta Neuropathol (Berl) 73:259–266
Ways P, Hanahan DJ (1964) Characterization and quantification of red cell lipid in normal man. J Lipid Res 5:318–328
Wiśniewski HM, Keith AB (1977) Chronic relapsing experimental allergic encephalomyelitis. An experimental model of multiple sclerosis. Ann Neurol 1:144–148
Author information
Authors and Affiliations
Additional information
Supported by the Intractable Disease Division, Public Health Bureau, Japanese Ministry of Health and Welfare, the grants (61570385, 63570363) from Japanese Ministry of Education
Rights and permissions
About this article
Cite this article
Tsukada, N., Koh, C.S., Yanagisawa, N. et al. Autoimmune encephalomyelitis in rhesus monkeys induced by immunization with cerebral endothelial cell membrane. Acta Neuropathol 77, 39–46 (1988). https://doi.org/10.1007/BF00688241
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00688241