Haptoglobin buffers lipopolysaccharides to delay activation of NFκB
It has remained yet unclear which soluble factors regulate the anti-inflammatory macrophage phenotype observed in both homeostasis and tumourigenesis. We show here that haptoglobin, a major serum protein with elusive immunoregulatory properties, binds and buffers bacterial lipopolysaccharides to...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Philipps-Universität Marburg
2024
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| Subjects: | |
| Online Access: | PDF Full Text |
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| Summary: | It has remained yet unclear which soluble factors regulate the anti-inflammatory
macrophage phenotype observed in both homeostasis and tumourigenesis. We
show here that haptoglobin, a major serum protein with elusive
immunoregulatory properties, binds and buffers bacterial lipopolysaccharides
to attenuate activation of NFkB in macrophages. Haptoglobin binds different
lipopolysaccharides with low micromolar affinities. Given its abundance,
haptoglobin constitutes a buffer for serum-borne lipopolysaccharides,
shielding them to safeguard against aberrant inflammatory reactions by
reducing the amount of free lipopolysaccharides available for binding to TLR4.
Concordantly, NFkB activation by haptoglobin-associated lipopolysaccharides
was markedly delayed relative to stimulation with pure lipopolysaccharide. Our
findings warrant evaluation of therapeutic benefits of haptoglobin for
inflammatory conditions and re-evaluation of purification strategies. Finally,
they allow to elucidate mechanisms of enhanced immunosuppression by
oncofetal haptoglobin. |
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| Item Description: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
| DOI: | 10.3389/fimmu.2024.1401527 |