Binding of Interferon Γ by Glycosaminoglycans: A Strategy for Localization and/or Inhibition of Its Activity

Fernández-Botrán, Rafael; Yan, Jun; Justus, David E.

doi:10.1006/cyto.1998.0438

Cited by 41 publications

(27 citation statements)

References 42 publications

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“…In the present study, we have demonstrated, for the first time, that dermatan sulfate on the surface of a motile cell type (mast cells) can bind IFN-␥ and present it to macrophages, inducing an immunologically important response. Consistent with our findings, it has recently been shown that C-terminal basic peptides of murine IFN-␥ interact with heparin, heparan sulfate, and chondroitin sulfate (16). Chondroitin sulfate has also been implicated in the biology of other cytokines and growth factors: chondroitin sulfate B (dermatan sulfate) binds IL-7, IL-12, IL-6, IL-1␣ and -␤, and human hepatocyte growth factor; promotes fibroblast growth factor-2 function; and regulates heparin affin regulatory peptide activity (37, 40 -42).…”

Section: Discussionsupporting

confidence: 93%

“…Utilizing endothelial cell layers and immobilized purified GAGs, others have shown that human IFN-␥ binds to heparin, heparan sulfate, and chondroitin sulfate, sulfation of the GAGs being essential for in this interaction (12)(13)(14)(15)(16)39). Binding is thought to be an ionic interaction between positively charged basic amino acids near the C terminus of IFN-␥ and the negatively charged sugar residues on GAGs (16).…”

Section: Discussionmentioning

confidence: 99%

“…Binding is thought to be an ionic interaction between positively charged basic amino acids near the C terminus of IFN-␥ and the negatively charged sugar residues on GAGs (16). The biological activity of IFN-␥ bound to immobilized GAGs or endothelium has been inferred by some and demonstrated by others (12, 14 -16).…”

Section: Discussionmentioning

confidence: 99%

“…One possible candidate is cell surface proteoglycans. In common with other cytokines and growth factors, human IFN-␥ has been shown to bind to proteoglycans of the extracellular matrix, and more specifically to the glycosaminoglycans (GAGs) heparin, heparan sulfate, and chondroitin sulfate (12)(13)(14)(15)(16). The binding interaction between human IFN-␥ and heparan sulfate has been well characterized: it involves two groups of carboxyl-terminal basic amino acids on the cytokine and two sulfated domains of heparan sulfate, such that the two domains of the GAG directly bind the two carboxyl-terminals of an IFN-␥ dimer (13,(17)(18)(19).…”

mentioning

confidence: 99%

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Presentation of IFN-γ to Nitric Oxide-Producing Cells: A Novel Function for Mast Cells

Brooks¹,

Briggs²,

Eastmond³

et al. 2000

The Journal of Immunology

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We report that mast cells can bind and present IFN-γ in a functionally active form to macrophages. Flow-cytometric analysis revealed that biotinylated IFN-γ bound equally well to purified peritoneal mast cells from both IFN-γR knockout and wild-type mice, indicating a non-IFN-γR binding site. Purified peritoneal mast cells, loaded with IFN-γ for 30 min and washed, were able to induce NO synthesis by peritoneal macrophages. This response required cell contact and expression of IFN-γR on the responding macrophages, but not the mast cells. Human HMC-1 mast cells were also able to present IFN-γ to mouse macrophages. Enzyme treatment of mouse mast cells revealed that binding of IFN-γ was predominantly to chondroitin sulfate B (dermatan sulfate). Binding of IFN-γ to dermatan sulfate was confirmed by inhibition ELISA. This study demonstrates for the first time that mast cells can present IFN-γ to other cells via glycosaminoglycans. Mast cells may act as a reservoir of surface-stored functionally active cytokines.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Presentation of IFN-γ to Nitric Oxide-Producing Cells: A Novel Function for Mast Cells

Brooks¹,

Briggs²,

Eastmond³

et al. 2000

The Journal of Immunology

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“…STAT activation could be blocked with IL-26-specific polyclonal antibodies from rabbit and goat, and by low concentrations of heparin, which presumably competes with surface proteoglycans for IL-26 binding at low concentrations (1 unit/ml or 5 g/ml heparin). Similar concentrations of heparin (4 g/ml) were described to inhibit IFN-␥ binding to Colo-205 cells by 50%, whereas IL-10 effects were reduced by 50% with 20 -100-fold higher heparin concentrations (42,44). Thus, IL-26 seems to utilize a mechanism that has been postulated before for IL-10 and IFN-␥ (Ref.…”

Section: Discussionmentioning

confidence: 52%

The T-cell Lymphokine Interleukin-26 Targets Epithelial Cells through the Interleukin-20 Receptor 1 and Interleukin-10 Receptor 2 Chains

Hör

Pirzer

Dumoutier

et al. 2004

Journal of Biological Chemistry

124

116

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Proteoglycans: Key Regulators of Pulmonary Inflammation and the Innate Immune Response to Lung Infection

Gill

Wight²,

Frevert

2010

The Anatomical Record

102

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Exposure to viruses and bacteria results in lung infections and places a significant burden on public health. The innate immune system is an early warning system that recognizes viruses and bacteria, which results in the rapid production of inflammatory mediators such as cytokines and chemokines and the pulmonary recruitment of leukocytes. When leukocytes emigrate from the systemic circulation through the extracellular matrix in response to lung infection they encounter proteoglycans, which consist of a core protein and their associated glycosaminoglycans. In this review, we discuss how proteoglycans serve to modify the pulmonary inflammatory response and leukocyte migration through a number of different mechanisms including: 1) The ability of soluble proteoglycans or fragments of glycosaminoglycans to activate Toll-like receptor signaling pathways; 2) The binding and sequestration of cytokines, chemokines, and growth factors by proteoglycans; 3) the ability of proteoglycans and hyaluronan to facilitate leukocyte adhesion and sequestration; and 4) The interactions between proteoglycans and matrix metalloproteinases that alter the function of these proteases. In conclusion, proteoglycans fine-tune tissue inflammation through a number of different mechanisms. Clarification of the mechanisms whereby proteoglycans modulate the pulmonary inflammatory response will most likely lead to new therapeutic approaches to inflammatory lung disease and lung infection.

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Binding of Interferon Γ by Glycosaminoglycans: A Strategy for Localization and/or Inhibition of Its Activity

Cited by 41 publications

References 42 publications

Presentation of IFN-γ to Nitric Oxide-Producing Cells: A Novel Function for Mast Cells

Presentation of IFN-γ to Nitric Oxide-Producing Cells: A Novel Function for Mast Cells

The T-cell Lymphokine Interleukin-26 Targets Epithelial Cells through the Interleukin-20 Receptor 1 and Interleukin-10 Receptor 2 Chains

Proteoglycans: Key Regulators of Pulmonary Inflammation and the Innate Immune Response to Lung Infection

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