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Sulfated glucuronyl paragloboside in rat brain microvessels
N Miyatani1, T Kohriyama, Y Maeda
1Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Richmond 23298-0614.
Abstract:
In patients with neuropathy associated with paraproteinemia, there are monoclonal immunoglobulin M antibodies reacting with myelin-associated glycoprotein and sulfated glucuronyl glycolipids. There are indications that the monoclonal antibodies may be responsible for these neuropathies. However, the mechanism by which the antibodies gain access to the nervous tissue, which is separated by the blood-brain barrier or blood-nerve barrier, is still unknown. In this study, we examined the presence of the sulfated glucuronyl glycolipid antigens on brain endothelial cells. Microvessels were isolated from adult Lewis rat brain cortex. Sulfated glucuronyl paragloboside (SGPG) was detected in the acidic lipid fraction by a TLC immunostaining method. Immunofluorescence studies showed positive staining on the surface of microvessels. In addition, SGPG could be detected in the cultured endothelial cells of human umbilical vein. These findings suggest that the endothelial cells contain antigenic sites for interaction with the autoantibodies. This type of interaction may result in damages to the endothelial cell function and may be responsible for changes in the blood-brain barrier permeability and the ensuing penetration of large molecules, such as immunoglobulins, into the endoneurial space.
Insights
Monoclonal antibodies in paraproteinemic neuropathy may target brain endothelial cells. This interaction could breach the blood-brain barrier, allowing immunoglobulin entry and nerve damage.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Glycosphingolipid Biochemistry
Background:
- Neuropathy associated with paraproteinemia involves monoclonal IgM antibodies targeting myelin-associated glycoprotein and sulfated glucuronyl glycolipids.
- The mechanism of autoantibody access to nervous tissue across the blood-brain barrier (BBB) or blood-nerve barrier (BNB) remains unclear.
Purpose of the Study:
- To investigate the presence of sulfated glucuronyl glycolipid antigens on brain endothelial cells.
- To explore a potential mechanism for autoantibody penetration into the central nervous system.
Main Methods:
- Isolation of microvessels from adult Lewis rat brain cortex.
- Detection of sulfated glucuronyl paragloboside (SGPG) using thin-layer chromatography (TLC) immunostaining.
- Immunofluorescence studies on microvessels and cultured human umbilical vein endothelial cells.
Main Results:
- SGPG was identified in the acidic lipid fraction of rat brain microvessels.
- Positive immunofluorescence staining for SGPG was observed on the surface of isolated microvessels.
- SGPG was also detected in cultured human umbilical vein endothelial cells.
Conclusions:
- Endothelial cells possess antigenic sites (SGPG) capable of interacting with autoantibodies.
- This interaction may impair endothelial cell function, altering BBB permeability.
- Increased BBB permeability could facilitate immunoglobulin entry into the endoneurial space, contributing to neuropathy.