Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 16800 |
| Fachzeitschrift | Scientific reports |
| Jahrgang | 5 |
| Publikationsstatus | Veröffentlicht - 19 Nov. 2015 |
Abstract
Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1-42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1-42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages.
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in: Scientific reports, Jahrgang 5, 16800, 19.11.2015.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages
AU - Shahraz, Anahita
AU - Kopatz, Jens
AU - Mathy, Rene
AU - Kappler, Joachim
AU - Winter, Dominic
AU - Kapoor, Shoba
AU - Schütza, Vlad
AU - Scheper, Thomas
AU - Gieselmann, Volkmar
AU - Neumann, Harald
N1 - Funding information: This project was supported by the DFG (FOR1336, KFO177, SFB704) and the Hertie foundation. H.N is member of the DFG-funded excellence cluster ‘ImmunoSensation’ (EXC 1023). This project was kindly supported by a grant from Bayer Pharma AG (‘from targets to novel drugs’ 2014-08-1139). We very much thank Rita Gerady-Schahn and Ajit Varki for helpful comments and open discussions. We thank Veit Hornung for kindly provide us THP monocytes. We thank WiCell for providing us iPS (Foreskin)-1 cells25. We thank Jessica Reinartz and Rita Jietou for excellent technical support.
PY - 2015/11/19
Y1 - 2015/11/19
N2 - Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1-42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1-42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages.
AB - Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1-42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1-42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages.
UR - http://www.scopus.com/inward/record.url?scp=84947577063&partnerID=8YFLogxK
U2 - 10.1038/srep16800
DO - 10.1038/srep16800
M3 - Article
C2 - 26582367
AN - SCOPUS:84947577063
VL - 5
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
M1 - 16800
ER -