Intravenous immunoglobulin preparations contain anti–Siglec-8 autoantibodies

Gunten, Stephan von; Vogel, Monique; Schaub, Alexander; Stadler, Beda M.; Miescher, Sylvia; Crocker, Paul R.; Simon, Hans‐Uwe

doi:10.1016/j.jaci.2007.01.023

Cited by 94 publications

(82 citation statements)

References 25 publications

(42 reference statements)

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“…Purified eosinophils were cultured for 24 or 72 h in interleukin 5 (IL-5) (10 ng/ml, R&D Systems), and then either 10 g/ml 2C4 antibody or 10 g/ml 2000-kDa PAA polymers were added for an additional 24 h. None of the cultures was performed without IL-5 because cytokine exposure is needed to see apoptosis to Siglec-8 antibodies alone (Nutku et al, 2003;von Gunten et al, 2007;Nutku-Bilir et al, 2008). Thus, no secondary antibodies were included.…”

Section: Methodsmentioning

confidence: 99%

Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6′-Sulfated Sialyl Lewis X

Hudson¹,

Bovin²,

Schnaar³

et al. 2009

J Pharmacol Exp Ther

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Section: Methodsmentioning

confidence: 99%

Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6′-Sulfated Sialyl Lewis X

Hudson¹,

Bovin²,

Schnaar³

et al. 2009

J Pharmacol Exp Ther

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“…It is known that neutrophils stimulated by inflammatory mediators, in comparison with their quiescent counterparts, exhibit different sensitivity to certain cell death-promoting stimuli (22,24,30), including soluble IgG preparations (IVIG) (11,12,15). Schettini et al (20) reported that immobilized IgA, but not soluble, plasma, or secretory IgA, promotes apoptosis of unstimulated neutrophils through a mechanism that is dependent on Mac-1 and involves respiratory burst activation.…”

Section: Immobilized Iga1 and Iga2 Trigger Fcari-mediated Neutrophil mentioning

confidence: 99%

“…Granulocyte death regulation was identified as one anti-inflammatory mechanism of high-dose i.v. Ig (IVIG) treatment, which is predominantly composed of pooled IgG (10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Human IgA Fc Receptor FcαRI (CD89) Triggers Different Forms of Neutrophil Death Depending on the Inflammatory Microenvironment

Wehrli

Cortinas-Elizondo

Hlushchuk

et al. 2014

The Journal of Immunology

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FcαRI (CD89), the human Fc receptor for IgA, is highly expressed on neutrophil granulocytes. In this study, we show that FcαRI induces different forms of neutrophil death, depending on the inflammatory microenvironment. The susceptibility of inflammatory neutrophils from sepsis or rheumatoid arthritis toward death induced by specific mAb, or soluble IgA at high concentrations, was enhanced. Although unstimulated cells experienced apoptosis following anti-FcαRI mAb stimulation, preactivation with cytokines or TLR agonists in vitro enhanced FcαRI-mediated death by additional recruitment of caspase-independent pathways, but this required PI3K class IA and MAPK signaling. Transmission electron microscopy of FcαRI-stimulated cells revealed cytoplasmic changes with vacuolization and mitochondrial swelling, nuclear condensation, and sustained plasma membrane. Coculture experiments with macrophages revealed anti-inflammatory effects of the partially caspase-independent death of primed cells following FcαRI engagement. Our data suggest that FcαRI has the ability to regulate neutrophil viability and to induce different forms of neutrophils depending on the inflammatory microenvironment and specific characteristics of the ligand–receptor interactions. Furthermore, these findings have potential implications for FcαRI-targeted strategies to treat neutrophil-associated inflammatory diseases.

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“…It has been shown that Siglecs play an important role in the internalization of sialic acid-expressing pathogens (17)(18)(19), in controlling allergic asthma (20,21), and in self-tolerance (22). Previously, we found that Siglec G/10-CD24 interaction selectively represses the NF-B-driven inflammatory response to danger-associated molecular patterns (DAMPs), 2 but not pathogen-associated molecular patterns (PAMPs) (23,24).…”

mentioning

confidence: 99%

Induction of Siglec-1 by Endotoxin Tolerance Suppresses the Innate Immune Response by Promoting TGF-β1 Production

Lan

Ren

et al. 2016

Journal of Biological Chemistry

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Sepsis is one of the leading causes of death worldwide. Although the prevailing theory for the sepsis syndrome is a condition of uncontrolled inflammation in response to infection, sepsis is increasingly being recognized as an immunosuppressive state known as endotoxin tolerance. We found sialylation of cell surface was significantly increased on LPS-induced tolerant cells; knockdown of Neu1 in macrophage cell line RAW 264.7 cells resulted in enhanced LPS-induced tolerance, whereas overexpression of Neu1 or treatment with sialidase abrogated LPS-induced tolerance, as defined by measuring TNF-␣ levels in the culture supernatants. We also found that the expression of Siglec-1 (a member of sialic acid-binding Ig (I)-like lectin family members, the predominant sialic acid-binding proteins on cell surface) was specifically up-regulated in endotoxin tolerant cells and the induction of Siglec-1 suppresses the innate immune response by promoting TGF-␤1 production. The enhanced TGF-␤1 production by Siglec-1 was significantly attenuated by spleen tyrosine kinase (Syk) inhibitor. Knockdown of siglec-1 in RAW 264.7 cells resulted in inhibiting the production of TGF-␤1 by ubiquitin-dependent degradation of Syk. Mechanistically, Siglec-1 associates with adaptor protein DNAX-activation protein of 12 kDa (DAP12) and transduces a signal to Syk to control the production of TGF-␤1 in endotoxin tolerance. Thus, Siglec-1 plays an important role in the development of endotoxin tolerance and targeted manipulation of this process could lead to a new therapeutic opportunity for patients with sepsis.Sepsis is generally defined as a systemic inflammatory response syndrome in response to infection. Sepsis can be potentially life threatening; of more than 1 million Americans who are diagnosed with severe sepsis every year, between 28 and 50% will die from this disease (1, 2). It is well-recognized that patients with sepsis are often immune suppressed, a state of reduced responsiveness to endotoxin known as endotoxin tolerance, deaths in this immunosuppressive phase are typically due to failure to control the secondary infections (3-5). The molecular mechanisms underlying this endotoxin tolerance phenomenon is poorly understood.Sialic acids are a family of nine-carbon acidic monosaccharides and are involved in immune response, such as host-pathogen recognition, migration, and antigen presentation. Mounting experimental evidence suggests that the presence of sialic acid residue act as a marker of self in the immune system, as such residues are absent from most microbes (6). Indeed, host cells can be lysed by immune cytotoxic effector mechanisms after extensive desialylation, an observation that demonstrates the significant role played by cell surface sialic acids in the selfrecognition process (7). In addition, normal human serum contains natural antibodies to sialidase-treated red blood cells (7-9), lymphocytes (10), and thymocytes (7). Recently, Meesmann et al. showed that desialylation acted as an "eat me" signal and caused an enhanced upt...

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Intravenous immunoglobulin preparations contain anti–Siglec-8 autoantibodies

Cited by 94 publications

References 25 publications

Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6′-Sulfated Sialyl Lewis X

Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6′-Sulfated Sialyl Lewis X

Human IgA Fc Receptor FcαRI (CD89) Triggers Different Forms of Neutrophil Death Depending on the Inflammatory Microenvironment

Induction of Siglec-1 by Endotoxin Tolerance Suppresses the Innate Immune Response by Promoting TGF-β1 Production

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