Keratan sulfate

About: Keratan sulfate is a research topic. Over the lifetime, 1253 publications have been published within this topic receiving 57984 citations. The topic is also known as: keratan sulfate & KS.

Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony-stimulating factors.

Abstract: Resident microglia of the rat CNS express a unique type of keratan sulfate immunoreactivity (KS-IR) that is lacking on peripheral monocytes/macrophages and associated with a so far unknown proteoglycan core protein. Microglial KS-IR is downregulated during T-cell-mediated autoimmune inflammation but largely preserved in degenerative lesion paradigms. This study addresses the role of cytokines and colony-stimulating factors in the regulation of microglial KS-IR. In vitro, ramified microglia in coculture with astrocytes, but not isolated microglia, constitutively expressed KS-IR under control conditions. In both culture paradigms, KS-IR was increased significantly by macrophage- (M-CSF) and granulocyte/macrophage colony-stimulating factors (GM-CSF), as well as tumor necrosis factor-α (TNF-α). By contrast, the Th1 cytokine interferon-γ (IFN-γ) downregulated KS-IR, both when applied alone or in combination with either GM-CSF, M-CSF, or TNF-α. In vivo, the intracerebroventricular administration of IFN-γ, but not TNF-α, to healthy rats led to an almost complete disappearance of KS-IR from ramified brain microglia. Our data suggest that the expression of microglial KS-IR is under dominant negative control by the Th1 cell cytokine IFN-γ and represent the first evidence of cytokine-dependent proteoglycan regulation in the CNS. GLIA 30:401–410, 2000. © 2000 Wiley-Liss, Inc.

Regulation of corneal inflammation by neutrophil‐dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient

Abstract: Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2 / corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan / and lumican / mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation. J. Leukoc. Biol. 88: 517–522; 2010.

Glycosaminoglycans produced in tissue culture by rat lung cells. Isolation from a mixed cell line and a derived endothelial clone.

Abstract: The glycosaminoglycans produced by a mixed cell line of normal adult rat lung and an endothelial clone derived from this line were isolated and examined. Cellulose acetate electrophoresis of media and cells before and after digestion with specific enzymes indicated that all the major glycosaminoglycans except keratan sulfate were synthesized by both cultures. Heparan sulfate and dermatan sulfate were found only in the cell fraction while hyaluronic acid was found in both the medium and the cell fractions. The chondroitin sulfates were isolated from the medium.The endothelial clone produced a 4: 1 ratio of glucosamine to galactosamine in the medium from the fifth through thirteenth months of culture. The medium of the mixed cell line initially contained glycosaminoglycans with a glucosamine to galactosamine ratio of 2:1 but after approximately one year of culture, the ratio had changed to 4.6: 1 suggesting that the culture contained predominantly endothelial cells.

Differential immunogold localisation of sulphated and unsulphated keratan sulphate proteoglycans in normal and macular dystrophy cornea using sulphation motif-specific antibodies.

Abstract: Keratan sulphate (KS) proteoglycans (PGs) are key molecules in the corneal stroma for tissue organisation and transparency. Macular corneal dystrophy (MCD) is a rare, autosomal recessive disease characterised by disturbances in KS expression. MCD is caused by mutations in CHST6, a gene encoding the enzyme responsible for KS sulphation. Sulphated KS is absent in type I disease causing corneal opacity and loss of vision. Genetic studies have highlighted the mutational heterogeneity in MCD, but supportive immunohistochemical studies on corneal KS have previously been limited by the availability of antibodies mostly reactive only with highly sulphated KS epitopes. In this study, we employed four antibodies against specific KS sulphation patterns, including one against unsulphated KS, to investigate their reactivity in a case of MCD compared with normal cornea using high-resolution immunogold electron microscopy. Mutation analysis indicated type I MCD with deletion of the entire open reading frame of CHST6. Contrast enhanced fixation revealed larger PG structures in MCD than normal. Unlike normal cornea, MCD cornea showed positive labelling with antibody to unsulphated KSPG, but was negative with antibodies to sulphated KSPG. These antibodies will thus facilitate high-resolution investigations of phenotypic heterogeneity in support of genetic studies in this disease.