Abstract
Objectives and Methods:Previous studies have demonstrated the involvement of glycosphingolipid (GSL) antigens in the pathogenesis of immune-mediated neurological disorders such as peripheral neuropathies and multiple sclerosis, as well as in infections of the central nervous system. We investigated the expression of neutral GSLs in the brain, thymus, spleen, and lungs of mice lacking the gene for the β<sub>2</sub>-microglobulin (β<sub>2</sub>M), an important component of the MHC class I molecule. Determination of GSL fractions in the tissues of mice homozygous (β<sub>2</sub>M–/–) or heterozygous (β<sub>2</sub>M+/–) for β<sub>2</sub>M gene knockout was performed by high performance thin layer chromatography, followed by immunostaining with specific antibodies. Results: Immunochemical analyses revealed abundant expression of globotetraosylceramide (Gb4), in the brain of β<sub>2</sub>M–/– mice, compared with undetectable expression in the control β<sub>2</sub>M+/– mice. The brain of both groups of animals was negative for Gg3, Gg4 and Gb3 immunostaining. Abundant expression of Gg3, Gg4, and Gb3 was found in the lungs of control β<sub>2</sub>M+/– mice, whereas β<sub>2</sub>M–/– mice lacked these structures. Immunostaining of Gb4 in the lungs was similar in both groups of animals. The thymus and spleen neutral GSL profiles did not significantly differ between β<sub>2</sub>M–/– and control animals. Conclusion: This study provides in vivoevidence that globo- and ganglio-series neutral GSL expression in the brain and lungs may be related to the presence of β<sub>2</sub>M or functional MHC class I molecule, and implicates different modulation of biosynthesis of globo- and ganglio-series neutral GSLs in these tissues.
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