Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion

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 Immler; Markus Moser; Uwe Koedel; Sandra Gran; Rodger P. McEver; Dietmar Vestweber; Admar Verschoor; Tomas Leanderson; Triantafyllos Chavakis; Johannes Roth; Thomas Vogl; Markus Sperandio

doi:10.1038/ncomms7915

Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion

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 Immler, Markus Moser, Uwe Koedel, Sandra Gran, Rodger P. McEver, Dietmar Vestweber, Admar Verschoor, Tomas Leanderson, Triantafyllos Chavakis, Johannes RothThomas Vogl, Markus Sperandio^*

^*Corresponding author for this work

Institute of Systemic Inflamation Research

81 Citations (Scopus)

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 β 22 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.

Original language	English
Article number	6915
Journal	Nature Communications
Volume	6
ISSN	1751-8628
DOIs	https://doi.org/10.1038/ncomms7915
Publication status	Published - 20.04.2015

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Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Pruenster, M., Kurz, A. R. M., Chung, K. J., Cao-Ehlker, X., Bieber, S., Nussbaum, C. F., Bierschenk, S., Eggersmann, T. K., Rohwedder, I., Heinig, K., Immler, R., Moser, M., Koedel, U., Gran, S., McEver, R. P., Vestweber, D., Verschoor, A., Leanderson, T., Chavakis, T., ... Sperandio, M. (2015). Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion. Nature Communications, 6, Article 6915. https://doi.org/10.1038/ncomms7915

@article{9b95f2bc11e74de3be3fd5b7cb1e2f6a,

title = "Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion",

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 β 22 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.",

author = "Monika Pruenster and Kurz, {Angela R.M.} and Chung, {Kyoung Jin} and Xiao Cao-Ehlker and Stephanie Bieber and Nussbaum, {Claudia F.} and Susanne Bierschenk and Eggersmann, {Tanja K.} and Ina Rohwedder and Kristina Heinig and Roland Immler and Markus Moser and Uwe Koedel and Sandra Gran and McEver, {Rodger P.} and Dietmar Vestweber and Admar Verschoor and Tomas Leanderson and Triantafyllos Chavakis and Johannes Roth and Thomas Vogl and Markus Sperandio",

note = "Funding Information: We thank Nadine Schmidt for technical assistance. This work was supported by Deutsche Forschungsgemeinschaft DFG - CRC914, project A1 (MM), B1 (MS) and B4 (AV), the EU-Project TARKINAID FP7-Health.2011.1.4.5 #282095 (MS), the European Research Council (281296-ENDHOMRET to TC), by Grants from the Interdisciplinary Center of Clinical Research of the University of Muenster (Vo2/014/09 and Ro2/003/15) and CRC 1009 B8 and B9 to T.V. and J.R, from the E-RARE2 Program Treat-AID to J.R. and by the Federal Ministry of Education and Research (BMBF), project AID-NET to J.R. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.",

year = "2015",

month = apr,

day = "20",

doi = "10.1038/ncomms7915",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "1751-8628",

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Pruenster, M, Kurz, ARM, Chung, KJ, Cao-Ehlker, X, Bieber, S, Nussbaum, CF, Bierschenk, S, Eggersmann, TK, Rohwedder, I, Heinig, K, Immler, R, Moser, M, Koedel, U, Gran, S, McEver, RP, Vestweber, D, Verschoor, A, Leanderson, T, Chavakis, T, Roth, J, Vogl, T & Sperandio, M 2015, 'Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion', Nature Communications, vol. 6, 6915. https://doi.org/10.1038/ncomms7915

TY - JOUR

T1 - Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion

AU - Pruenster, Monika

AU - Kurz, Angela R.M.

AU - Chung, Kyoung Jin

AU - Cao-Ehlker, Xiao

AU - Bieber, Stephanie

AU - Nussbaum, Claudia F.

AU - Bierschenk, Susanne

AU - Eggersmann, Tanja K.

AU - Rohwedder, Ina

AU - Heinig, Kristina

AU - Immler, Roland

AU - Moser, Markus

AU - Koedel, Uwe

AU - Gran, Sandra

AU - McEver, Rodger P.

AU - Vestweber, Dietmar

AU - Verschoor, Admar

AU - Leanderson, Tomas

AU - Chavakis, Triantafyllos

AU - Roth, Johannes

AU - Vogl, Thomas

AU - Sperandio, Markus

N1 - Funding Information: We thank Nadine Schmidt for technical assistance. This work was supported by Deutsche Forschungsgemeinschaft DFG - CRC914, project A1 (MM), B1 (MS) and B4 (AV), the EU-Project TARKINAID FP7-Health.2011.1.4.5 #282095 (MS), the European Research Council (281296-ENDHOMRET to TC), by Grants from the Interdisciplinary Center of Clinical Research of the University of Muenster (Vo2/014/09 and Ro2/003/15) and CRC 1009 B8 and B9 to T.V. and J.R, from the E-RARE2 Program Treat-AID to J.R. and by the Federal Ministry of Education and Research (BMBF), project AID-NET to J.R. Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.

PY - 2015/4/20

Y1 - 2015/4/20

N2 - 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 β 22 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.

AB - 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 β 22 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.

UR - http://www.scopus.com/inward/record.url?scp=84928486388&partnerID=8YFLogxK

U2 - 10.1038/ncomms7915

DO - 10.1038/ncomms7915

M3 - Journal articles

C2 - 25892652

AN - SCOPUS:84928486388

SN - 1751-8628

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6915

ER -

Extracellular MRP8/14 is a regulator of β22 integrin-dependent neutrophil slow rolling and adhesion

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