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Directional Mast Cell Degranulation of TNF into Blood Vessels Primes Neutrophil Extravasation

50 Pages Posted: 7 Aug 2020 Publication Status: Published

See all articles by Jan Dudeck

Jan Dudeck

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Johanna Kotrba

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Roland Immler

Ludwig Maximilian University of Munich (LMU) - Institute of Cardiovascular Physiology and Pathophysiology

Aaron Hoffmann

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Martin Voss

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Vasileia Ismini Alexaki

Technical University of Dresden - Institute of Clinical Chemistry and Laboratory Medicine

Lorena Morton

Otto-von-Guericke-Universität Magdeburg - Institute for Inflammation and Neurodegeneration

Stephan René Jahn

Technical University of Dresden - Institute for Immunology

Simon Winzer

Technical University of Dresden - Institute for Immunology

George Kollias

Biomedical Sciences Research Centre (B.S.R.C.) “Alexander Fleming” - Department of Immunology

Thomas Fischer

Otto-von-Guericke-Universität Magdeburg - Health Campus Immunology, Infectiology and Inflammation

Sergei A. Nedospasov

Russian Academy of Sciences (RAS) - Engelhardt Institute of Molecular Biology

Ildiko Rita Dunay

Otto-von-Guericke-Universität Magdeburg - Institute for Inflammation and Neurodegeneration

Triantafyllos Chavakis

Technical University of Dresden - Institute of Clinical Chemistry and Laboratory Medicine

Andreas J. Mueller

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Burkhart Schraven

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

Markus Sperandio

Ludwig Maximilian University of Munich (LMU) - Institute of Cardiovascular Physiology and Pathophysiology

Anne Dudeck

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology

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Abstract

Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrate that MC-derived TNF is crucial for neutrophil extravasation to sites of sterile skin inflammation by promoting intraluminal adhesion and crawling. Strikingly, MC-TNF directly primes circulating neutrophils via TNFR1, while being dispensable for chemokine production and endothelial cell activation. The MC-TNF is fused into the bloodstream by directional degranulation of perivascular MCs that are part of the vascular unit with access to the vessel lumen. Consistently, intravenous administration of MC granules can boost neutrophil extravasation. Consequently, the directional MC degranulation of pro-inflammatory mediators into the bloodstream may represent an important target for therapeutic approaches aimed at dampening cytokine storm syndromes or shock symptoms, or intentionally pushing immune defense.

Keywords: mast cells, neutrophilextravasation, inflammation, TNF, degranulation, blood vessel

Suggested Citation

Dudeck, Jan and Kotrba, Johanna and Immler, Roland and Hoffmann, Aaron and Voss, Martin and Alexaki, Vasileia Ismini and Morton, Lorena and Jahn, Stephan René and Winzer, Simon and Kollias, George and Fischer, Thomas and Nedospasov, Sergei A. and Dunay, Ildiko Rita and Chavakis, Triantafyllos and Mueller, Andreas J. and Schraven, Burkhart and Sperandio, Markus and Dudeck, Anne, Directional Mast Cell Degranulation of TNF into Blood Vessels Primes Neutrophil Extravasation. Available at SSRN: https://ssrn.com/abstract=3651507 or http://dx.doi.org/10.2139/ssrn.3651507
This version of the paper has not been formally peer reviewed.

Jan Dudeck

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Johanna Kotrba

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Roland Immler

Ludwig Maximilian University of Munich (LMU) - Institute of Cardiovascular Physiology and Pathophysiology ( email )

Geschwister-Scholl-Platz 1
Munich, DE Bavaria 80539
Germany

Aaron Hoffmann

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Martin Voss

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Vasileia Ismini Alexaki

Technical University of Dresden - Institute of Clinical Chemistry and Laboratory Medicine ( email )

Helmholtzstraße 10, 01062 Dresden, Germany
Dresden, 01062
Germany

Lorena Morton

Otto-von-Guericke-Universität Magdeburg - Institute for Inflammation and Neurodegeneration ( email )

Universitätspl. 2
PSF 4120
Magdeburg, D-39106
Germany

Stephan René Jahn

Technical University of Dresden - Institute for Immunology ( email )

Helmholtzstraße 10, 01062 Dresden, Germany
Dresden, 01062
Germany

Simon Winzer

Technical University of Dresden - Institute for Immunology ( email )

Helmholtzstraße 10, 01062 Dresden, Germany
Dresden, 01062
Germany

George Kollias

Biomedical Sciences Research Centre (B.S.R.C.) “Alexander Fleming” - Department of Immunology ( email )

Greece

Thomas Fischer

Otto-von-Guericke-Universität Magdeburg - Health Campus Immunology, Infectiology and Inflammation ( email )

Universitätspl. 2
PSF 4120
Magdeburg, D-39106
Germany

Sergei A. Nedospasov

Russian Academy of Sciences (RAS) - Engelhardt Institute of Molecular Biology ( email )

Ildiko Rita Dunay

Otto-von-Guericke-Universität Magdeburg - Institute for Inflammation and Neurodegeneration ( email )

Universitätspl. 2
PSF 4120
Magdeburg, D-39106
Germany

Triantafyllos Chavakis

Technical University of Dresden - Institute of Clinical Chemistry and Laboratory Medicine ( email )

Helmholtzstraße 10, 01062 Dresden, Germany
Dresden, 01062
Germany

Andreas J. Mueller

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Burkhart Schraven

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

Markus Sperandio

Ludwig Maximilian University of Munich (LMU) - Institute of Cardiovascular Physiology and Pathophysiology ( email )

Geschwister-Scholl-Platz 1
Munich, DE Bavaria 80539
Germany

Anne Dudeck (Contact Author)

Otto-von-Guericke-Universität Magdeburg - Institute for Molecular and Clinical Immunology ( email )

Germany

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