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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1401527
This article is part of the Research Topic Cytokines and soluble mediators in reprogramming of tumor microenvironment View all 3 articles

Haptoglobin buffers lipopolysaccharides to delay activation of NFκB

Provisionally accepted
Laura Zein Laura Zein 1,2,3Josina Grossmann Josina Grossmann 1,2,4Helena Swoboda Helena Swoboda 1,2Christina Borgel Christina Borgel 1,2Bernhard Wilke Bernhard Wilke 1,2Stephan Awe Stephan Awe 5Andrea Nist Andrea Nist 6Thorsten Stiewe Thorsten Stiewe 6Oliver Stehling Oliver Stehling 7Sven-Andreas Freibert Sven-Andreas Freibert 7Till Adhikary Till Adhikary 8*Ho-Ryun Chung Ho-Ryun Chung 2*
  • 1 Institute for Molecular Biology and Tumor Research, Center for Tumor Biology and Immunology, Philipps University Marburg, Germany, Germany, Germany
  • 2 Institute for Medical Bioinformatics and Biostatistics, Philipps University Marburg, Marburg, Germany
  • 3 Institute for Experimental Cancer Research in Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany
  • 4 German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
  • 5 Institute for Molecular Biology and Tumor Research, Biomedical Research Center, Philipps University Marburg, Marburg, Germany
  • 6 Genomics Core Facility, Center for Tumor Biology and Immunology, Philipps University Marburg, Marburg, Germany
  • 7 Protein Biochemistry and Spectroscopy Core Facility, Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany
  • 8 University of Marburg, Marburg, Germany

The final, formatted version of the article will be published soon.

    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 NFκB 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, NFκB 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.

    Keywords: LPS, lipopolysaccharide, Haptoglobin, NFkB, LPS buffering

    Received: 15 Mar 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Zein, Grossmann, Swoboda, Borgel, Wilke, Awe, Nist, Stiewe, Stehling, Freibert, Adhikary and Chung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Till Adhikary, University of Marburg, Marburg, Germany
    Ho-Ryun Chung, Institute for Medical Bioinformatics and Biostatistics, Philipps University Marburg, Marburg, Germany

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