Expression of neutral glycosphingolipids in the brain, lymphoid organs and lungs of mice lacking beta(2)-microglobulin.
OBJECTIVE
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 beta(2)-microglobulin (beta(2)M), an important component of the MHC class I molecule. Determination of GSL fractions in the tissues of mice homozygous (beta(2)M-/-) or heterozygous (beta(2)M+/-) for beta(2)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 (Gb 4), in the brain of beta(2)M-/- mice, compared with undetectable expression in the control beta(2)M+/- mice. The brain of both groups of animals was negative for Gg 3, Gg 4 and Gb 3 immunostaining. Abundant expression of Gg 3, Gg 4, and Gb 3 was found in the lungs of control beta(2)M+/- mice, whereas beta(2)M-/- mice lacked these structures. Immunostaining of Gb 4 in the lungs was similar in both groups of animals. The thymus and spleen neutral GSL profiles did not significantly differ between beta(2)M-/- and control animals.


CONCLUSIONS
This study provides in vivo-evidence that globo- and ganglio-series neutral GSL expression in the brain and lungs may be related to the presence of beta(2)M or functional MHC class I molecule, and implicates different modulation of biosynthesis of globo- and ganglio-series neutral GSLs in these tissues.
Markotić
Anita
A
Department of Biochemistry, Split University School of Medicine, Split, Croatia. markotic@bsb.mefst
Marusić
Ana
A
Muthing
Johannes
J
D000818:Animals; D001923:Brain Chemistry / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020383:Neutral Glycosphingolipids / Q000096:biosynthesis*; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D020383:Neutral Glycosphingolipids; D001613:beta 2-Microglobulin