Glycosylation of interleukin-6 purified from normal human blood mononuclear cells.
Interleukin 6 (IL-6) is a glycosylated cytokine which is important in exerting cell-specific growth-inducing, growth-inhibiting and differentiation-inducing effects. IL-6 produced in mammalian cell lines is heterogeneous, reflecting specific cell-type-dependent post-translational modifications. Native IL-6 was purified from human blood mononuclear cells and the oligosaccharides released, radiolabelled and sequenced by a combination of sequential exoglycosidase digestion using Bio-Gel P-4 high-resolution gel chromatography and acetolysis. N- and O-linked glycans were found. The N-linked glycans were sialylated di- and tri-antennary complex-type and oligomannose-type structures. However, the most predominant N-linked oligosaccharide was a small tetrasaccharide with the sequence Man alpha 6Man beta 4GlcNAc beta 4GlcNAc. This is the first report of this structure on a circulating glycoprotein. This structure has only previously been reported to be present on the syncytiotrophoblast of human placenta. The presence of the oligomannose structures and the mannose-terminating tetrasaccharide on IL-6 may be important in maintaining a high local concentration of the cytokine while limiting its systemic serum level via interaction with soluble mannose-binding serum lectins.
Parekh
R B
RB
Department of Biochemistry, Oxford, England.
Dwek
R A
RA
Rademacher
T W
TW
Opdenakker
G
G
Van Damme
J
J
D002240:Carbohydrate Sequence; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D015850:Interleukin-6 / Q000302:isolation & purification / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
D015850:Interleukin-6