Histidine-Rich Glycoprotein Binds to DNA and FcγRI and Potentiates the Ingestion of Apoptotic Cells by Macrophages

Gorgani, Nick N.; Smith, Brian A.; Kono, Dwight H.; Theofilopoulos, Argyrios N.

doi:10.4049/jimmunol.169.9.4745

Cited by 47 publications

(55 citation statements)

References 55 publications

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“…Sequence-independent binding of CpG-containing ODN to lactoferrin decreases their cellular uptake and inhibits their immune stimulation (12), indicating that peptide-binding can suppress host responses driven by these potent adjuvants. Similarly, the histidine-rich glycoprotein, an abundant serum protein, binds DNA of apoptotic cells and the Fc␥RI on monocytes, thereby contributing to the antiinflammatory apoptotic cell clearance by macrophages (13). These findings suggest that peptide binding of nucleotides can attenuate their adjuvant activity.…”

Section: U Nmethylated Cpg Motifs Prevalent In Bacterial Genomicmentioning

confidence: 86%

Antigenic Epitopes Fused to Cationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4+ T Cell Help-Independent, Priming of CD8+ T Cells

Schirmbeck

Riedl

Zurbriggen

et al. 2003

The Journal of Immunology

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A priority in current vaccine research is the development of adjuvants that support the efficient priming of long-lasting, CD4+ T cell help-independent CD8+ T cell immunity. Oligodeoxynucleotides (ODN) with immune-stimulating sequences (ISS) containing CpG motifs facilitate the priming of MHC class I-restricted CD8+ T cell responses to proteins or peptides. We show that the adjuvant effect of ISS+ ODN on CD8+ T cell priming to large, recombinant Ag is enhanced by binding them to short, cationic (arginine-rich) peptides that themselves have no adjuvant activity in CD8+ T cell priming. Fusing antigenic epitopes to cationic (8- to 10-mer) peptides bound to immune-stimulating ISS+ ODN or nonstimulating NSS+ ODN (without CpG-containing sequences) generated immunogens that efficiently primed long-lasting, specific CD8+ T cell immunity of high magnitude. Different MHC class I-binding epitopes fused to short cationic peptides of different origins showed this adjuvant activity. Quantitative ODN binding to cationic peptides strikingly reduced the toxicity of the latter, suggesting that it improves the safety profile of the adjuvant. CD8+ T cell priming supported by this adjuvant was Toll-like receptor 9 dependent, but required no CD4+ T cell help. ODN (with or without CpG-containing sequences) are thus potent Th1-promoting adjuvants when bound to cationic peptides covalently linked to antigenic epitopes, a mode of Ag delivery prevailing in many viral nucleocapsids.

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Section: U Nmethylated Cpg Motifs Prevalent In Bacterial Genomicmentioning

confidence: 86%

Antigenic Epitopes Fused to Cationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4+ T Cell Help-Independent, Priming of CD8+ T Cells

Schirmbeck

Riedl

Zurbriggen

et al. 2003

The Journal of Immunology

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“…These reports do not necessarily infer causality, but they are fully compatible with a role of Ahsg in clearing insoluble remnants and cellular debris. It is interesting that a similar function in innate immunity has been recently demonstrated for a structurally related member of the cystatin superfamily of serum proteins, histidinerich glycoprotein (58).…”

Section: Discussionmentioning

confidence: 99%

The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

Schäfer¹,

Heiss²,

Schwarz³

et al. 2003

J. Clin. Invest.

799

535

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Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein α 2 -Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.

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“…The erythrocyte-free nucleated cell fraction was subjected to FACS analysis and fluorescent cell sorting to isolate GFP-expressing, RFP-expressing, or double positive yellow cells using previously described protocols. 16 Purified circulating human prostate carcinoma cells were immediately expanded in culture for biological assays and microarray analysis. Fluorescent microscopy analysis (see below) confirmed that resulting cell cultures contained at least 98% fluorescent cells.…”

Section: Methodsmentioning

confidence: 99%

Dual-Color-Coded Imaging of Viable Circulating Prostate Carcinoma Cells Reveals Genetic Exchange between Tumor Cells In Vivo, Contributing to Highly Metastatic Phenotypes

Glinsky¹,

Glinskii²,

Berezovskaya³

et al. 2005

Cell Cycle

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Histidine-Rich Glycoprotein Binds to DNA and FcγRI and Potentiates the Ingestion of Apoptotic Cells by Macrophages

Cited by 47 publications

References 55 publications

Antigenic Epitopes Fused to Cationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4+ T Cell Help-Independent, Priming of CD8+ T Cells

Antigenic Epitopes Fused to Cationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4+ T Cell Help-Independent, Priming of CD8+ T Cells

The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

Dual-Color-Coded Imaging of Viable Circulating Prostate Carcinoma Cells Reveals Genetic Exchange between Tumor Cells In Vivo, Contributing to Highly Metastatic Phenotypes

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