Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis.
Mechanisms involved in the loss of blood-brain barrier function in Lewis rats with experimental autoimmune encephalomyelitis (EAE) were examined using horseradish peroxidase (HRP) as a tracer. In animals injected with HRP before fixation, tracer was observed in two intracytoplasmic compartments: multivesicular bodies (presumably secondary lysosomes) and transcytotic vesicles. Quantitative morphometry of electron micrographs of capillary endothelial cells demonstrated a 5.2-fold increase in these vesicles. This increase in vesicular transport was associated with a decrease in mitochondrial content from 13.7% of the endothelial cytoplasmic area in the normal rat to 4.2% in EAE rats at the height of clinical disease. These alterations correlated with the clinical course of EAE. In animals infused with tracer after fixation, tracer was restricted to areas of cellular inflammation. Immunogold staining of endogenous albumin demonstrated the presence of albumin in cytoplasmic vesicles and in channel-like tubular structures adjacent to endothelial cell junctions. These results indicate that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE.
Claudio
L
L
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
Kress
Y
Y
Norton
W T
WT
Brosnan
C F
CF
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D001812:Blood-Brain Barrier; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006735:Horseradish Peroxidase; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D006735:Horseradish Peroxidase