Glycosylation of interleukin‐6 purified from normal human blood mononuclear cells

Abstract

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 Manα6Manβ4GlcNAcβ4GlcNAc. 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. Copyright © 1992, Wiley Blackwell. All rights reserved