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Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion

Author

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  • Monika Pruenster

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Angela R. M. Kurz

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Kyoung-Jin Chung

    (Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden)

  • Xiao Cao-Ehlker

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Stephanie Bieber

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Claudia F. Nussbaum

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Susanne Bierschenk

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Tanja K. Eggersmann

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Ina Rohwedder

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Kristina Heinig

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Roland Immler

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

  • Markus Moser

    (Max Planck Institute for Biochemistry)

  • Uwe Koedel

    (Ludwig-Maximilians Universität)

  • Sandra Gran

    (Institute of Immunology, University of Muenster)

  • Rodger P. McEver

    (Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation)

  • Dietmar Vestweber

    (Max Planck Institute for Biomolecular Medicine)

  • Admar Verschoor

    (Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität)

  • Tomas Leanderson

    (Immunology Group, University of Lund)

  • Triantafyllos Chavakis

    (Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden)

  • Johannes Roth

    (Institute of Immunology, University of Muenster)

  • Thomas Vogl

    (Institute of Immunology, University of Muenster)

  • Markus Sperandio

    (Institute of Cardiovascular Physiology and Pathophysiology, Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians Universität)

Abstract

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin–PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid β2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.

Suggested Citation

  • Monika Pruenster & Angela R. M. Kurz & Kyoung-Jin Chung & Xiao Cao-Ehlker & Stephanie Bieber & Claudia F. Nussbaum & Susanne Bierschenk & Tanja K. Eggersmann & Ina Rohwedder & Kristina Heinig & Roland, 2015. "Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7915
    DOI: 10.1038/ncomms7915
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