TY - JOUR
T1 - Interferon-γ alters expression of endothelial cell-surface glycosphingolipids
AU - Gillard, Baiba K.
AU - Jones, Mary A.
AU - Turner, Ann A.
AU - Lewis, Dorothy E.
AU - Marcus, Donald M.
N1 - Funding Information:
’ This work was supported by National Institutes search Grants HL 38788 and AI 17712. * To whom correspondence should be addressed.
PY - 1990/5/15
Y1 - 1990/5/15
N2 - Our previous work on human endothelial cell (EC) glycosphingolipids (GSLs) demonstrated that these cells contain a large diversity of GSLs, predominantly with lacto core structures. In order to evaluate the role of GSLs as EC antigens and receptors, we investigated their cell-surface expression on confluent EC monolayers and ECs activated by interferon-γ (IFN-γ) and interleukin-1 (IL-1). IFN-γ activation of endothelial cells resulted in a small change in GSL composition, but greatly increased surface expression of gangliosides and decreased surface expression of neutral GSLs. In particular, surface expression of the major neutral GSL, globoside, decreased three- to fourfold as measured both by galactose oxidase labeling and by binding of the anti-globoside monoclonal antibody 9G7. IFN-γ did not significantly alter the total cell content of globoside, as measured by metabolic labeling, but rather altered the ratio of accessible cell surface to intracellular globoside. Two mechanisms appear to contribute to the decreased cell-surface globoside expression. IFN-γ treatment increased the relative proportion of intracellular globoside which is associated with the cell cytoskeleton. IFN-γ treatment also caused more of the cell-surface globoside to be inaccessible to antibody, and both neuraminidase and trypsin treatment of the cells increased globoside accessibility. IL-1 treatment increased total cell GSL content, but did not alter GSL composition or cell-surface binding by six anti-carbohydrate antibodies. The specific modulation of cell-surface GSLs by IFN-γ suggests that GSLs may play a role in the altered adhesive and receptor activities of IFN-γ-activated ECS.
AB - Our previous work on human endothelial cell (EC) glycosphingolipids (GSLs) demonstrated that these cells contain a large diversity of GSLs, predominantly with lacto core structures. In order to evaluate the role of GSLs as EC antigens and receptors, we investigated their cell-surface expression on confluent EC monolayers and ECs activated by interferon-γ (IFN-γ) and interleukin-1 (IL-1). IFN-γ activation of endothelial cells resulted in a small change in GSL composition, but greatly increased surface expression of gangliosides and decreased surface expression of neutral GSLs. In particular, surface expression of the major neutral GSL, globoside, decreased three- to fourfold as measured both by galactose oxidase labeling and by binding of the anti-globoside monoclonal antibody 9G7. IFN-γ did not significantly alter the total cell content of globoside, as measured by metabolic labeling, but rather altered the ratio of accessible cell surface to intracellular globoside. Two mechanisms appear to contribute to the decreased cell-surface globoside expression. IFN-γ treatment increased the relative proportion of intracellular globoside which is associated with the cell cytoskeleton. IFN-γ treatment also caused more of the cell-surface globoside to be inaccessible to antibody, and both neuraminidase and trypsin treatment of the cells increased globoside accessibility. IL-1 treatment increased total cell GSL content, but did not alter GSL composition or cell-surface binding by six anti-carbohydrate antibodies. The specific modulation of cell-surface GSLs by IFN-γ suggests that GSLs may play a role in the altered adhesive and receptor activities of IFN-γ-activated ECS.
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U2 - 10.1016/0003-9861(90)90471-A
DO - 10.1016/0003-9861(90)90471-A
M3 - Article
C2 - 2110799
AN - SCOPUS:0025268087
SN - 0003-9861
VL - 279
SP - 122
EP - 129
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -