Haptoglobin buffers lipopolysaccharides to safeguard against aberrant NFκB activation

Zein, L.; Grossmann, J.; Swoboda, H.; Borgel, C.; Wilke, B.; Awe, S.; Nist, A.; Stiewe, T.; Stehling, O.; Freibert, S.-A.; Adhikary, T.; Chung, H.-R.

doi:10.1101/2022.11.22.516855

bioRxiv · 10.1101/2022.11.22.516855

Haptoglobin buffers lipopolysaccharides to safeguard against aberrant NFκB activation

Zein, L.·Grossmann, J.·Swoboda, H.·Borgel, C.·Wilke, B.·Awe, S.·Nist, A.·Stiewe, T.·Stehling, O.·Freibert, S.-A.·Adhikary, T.·Chung, H.-R.

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Abstract

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 pro-tein with elusive immunoregulatory properties, binds and buffers serum-borne bacterial lipopolysaccharides to attenuate activation of NF{kappa}B in macrophages. Haptoglobin binds different lipopolysaccharides with low micromolar affinities. Given its abundance, haptoglobin constitutes a buffer for lipopolysaccharides, shielding them to safeguard against aberrant inflammatory reactions caused by small fluctuations. Concordantly, NF{kappa}B activation by haptoglobin-associated lipopolysaccharides was 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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Zein, L., Grossmann, J., Swoboda, H., Borgel, C., Wilke, B., Awe, S., Nist, A., Stiewe, T., Stehling, O., Freibert, S.-A., Adhikary, T., Chung, H.-R.. 2022-11-22. Haptoglobin buffers lipopolysaccharides to safeguard against aberrant NFκB activation. https://doi.org/10.1101/2022.11.22.516855

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