Selective and differential binding of interleukin (IL)‐1α, IL‐1β, IL‐2 and IL‐6 to glycosaminoglycans

Ramsden, Lawrence; Rider, Christopher C.

doi:10.1002/eji.1830221139

Cited by 125 publications

(73 citation statements)

References 21 publications

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“…Interestingly, injection of IL-2-FP plus anti-CD4 mAb with the aim of depleting CD25 + CD4 + Tregs was not as efficient in stimulating memory CD8 + T cells in vivo as IL-2-FP plus anti-CD25 mAb. Finally, cytokines can also interact with components of the extracellular matrix (ECM), most notably heparan sulfate proteoglycans, which have been reported to bind various cytokines, including IL-1α, IL-1β, IL-2, IL-3, IL-6, IL-7, GM-CSF, and TGF-β1, in addition to chemokines and growth factors (40)(41)(42)(43)(44). Notably, anti-IL-2 mAbs might mediate some of their effects by influencing the binding of IL-2 to the ECM.…”

Section: Discussionmentioning

confidence: 99%

IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25

Létourneau

Leeuwen

Krieg

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

187

211

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IL-2 is crucial to T cell homeostasis, especially of CD4 + T regulatory cells and memory CD8 + cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor α (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.CD25 | cytokine | cytokine/mAb complexes | T cell homeostasis | Fc receptor

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Section: Discussionmentioning

confidence: 99%

IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25

Létourneau

Leeuwen

Krieg

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

187

211

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“…IL-6 is known to specifically bind to heparan sulfate glycosaminoglycan chains (53,54), and we show in this study that IL-6 binds to syndecan-1, which has been proposed to provide a mode of retaining IL-6 close to its site of secretion, thus favoring a paracrine mode of action (53). IL-6 can both inhibit or stimulate its own secretion depending on cell type; it is possible therefore that in the naive situation syndecan-1-bound IL-6 acts locally at the choroid plexus epithelium to inhibit its own secretion and that this inhibition is lifted when syndecan-1 is shed during EAE or is absent as in the Sdc-1 2/2 mouse.…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1, a Cell Surface Proteoglycan, Negatively Regulates Initial Leukocyte Recruitment to the Brain across the Choroid Plexus in Murine Experimental Autoimmune Encephalomyelitis

Zhang¹,

Wu²,

Song³

et al. 2013

The Journal of Immunology

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The cell surface heparan sulfate proteoglycan, syndecan-1, has been reported to be a negative regulator of various inflammatory processes, but its precise mode of action is poorly defined. In this study, we use the murine model of the 35–55 peptide of myelin oligodendrocyte glycoprotein–induced experimental autoimmune encephalomyelitis (EAE), a T lymphocyte–mediated inflammation where the steps in disease development and recovery are well characterized, to decipher how syndecan-1 impacts on the inflammatory reaction. Syndecan-1 knockout (Sdc-1−/−) mice show enhanced disease severity and impaired recovery. The use of bone marrow chimeric mice reveals that both an immune cell and a CNS-resident source of syndecan-1 contribute to this phenotype. Epithelial cells of the choroid plexus, where initial CCL20-induced leukocyte recruitment to the brain occurs, are identified as the predominant site of syndecan-1 expression. Syndecan-1 is lost from this site during the course of EAE by shedding into the cerebrospinal fluid, which correlates with loss of epithelial cell surface–bound CCL20 and is associated with the upregulation of IL-6 expression. In Sdc-1−/− mice, early leukocyte recruitment via the choroid plexus is enhanced, and IL-6 is elevated, which collectively results in higher numbers of the disease inducing Th17 cells in the CNS, thereby contributing to enhanced disease severity. Furthermore, Sdc-1−/− mice have intrinsically elevated plasma cell numbers and higher myelin oligodendrocyte glycoprotein–specific Ab levels during EAE, which we propose contributes to impaired recovery. Our data identify the choroid plexus epithelium as a novel source of IL-6 in EAE and demonstrate that its expression negatively correlates with syndecan-1 expression at this site.

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“…IL-1␤ partially binds to hyaluronic acid, whereas IL-1␣ shows essentially no retention. Selective, partial binding to acidic polysaccharides is also exhibited by IL-6, which binds heparin, dextran sulfate, and dermatan sulfate but is poorly retained on chondroitin sulfate [39,40].…”

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins

Bodo

Blasi²,

Becchetti³

et al. 1998

Journal of Leukocyte Biology

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Glycosaminoglycans (GAG), are extracellular matrix macromolecules that affect the phagocytic properties of macrophages. In order to assess whether the interaction between macrophages and Candida albicans (iCa) provokes changes in the phenotype, we analyzed the GAG profiles in two macrophage lines, ANA-1 (from murine bonemarrow) and BV-2 (from murine brain). We also investigated GAG modulation by interleukin-1␣ (IL-1␣) and interleukin-6 (IL-6). During iCa treatment and even after the addition of ILs, ANA-1 accumulated less total GAG compared to controls. IL-1 treatment, combined with iCa exposure, induced a decrease in heparan sulfate and chondroitin sulfate chains, and an increase in the hyaluronic acid percentage. IL-6 treatment, with or without iCa, decreased the hyaluronic acid/sulfated GAG ratio. The GAG pattern in BV-2 appears to be different to ANA-1 and iCa exposure does not induce any difference in total GAG. The inhibitory effect induced by ILs on GAG synthesis is less than that observed in ANA-1 and the GAG elution profile is modulated to a lesser extent by treatment with ILs and/or iCa compared to the ANA-1. We suggest that the observed changes in the expression of the individual GAG classes may be responsible for the macrophage functional heterogeneity. J. Leukoc. Biol. 64: 650-656; 1998.

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Selective and differential binding of interleukin (IL)‐1α, IL‐1β, IL‐2 and IL‐6 to glycosaminoglycans

Cited by 125 publications

References 21 publications

IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25

IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25

Syndecan-1, a Cell Surface Proteoglycan, Negatively Regulates Initial Leukocyte Recruitment to the Brain across the Choroid Plexus in Murine Experimental Autoimmune Encephalomyelitis

Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins

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