Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases

Hahn J, Schauer C, Czegley C, Kling L, Petru L, Schmid B, Weidner D, Reinwald C, Biermann MH, Blunder S, Ernst J, Lesner A, Bäuerle T, Palmisano R, Christiansen S, Herrmann M, Bozec A, Gruber R, Schett G, Hoffmann M (2018)

Publication Type: Journal article, Original article

Publication year: 2018

Journal

The FASEB Journal Federation of American Society of Experimental Biology (FASEB)

URI: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.201800752R

DOI: 10.1096/fj.201800752R

Abstract

Papillon-Lefèvre syndrome (PLS) is characterized by nonfunctional neutrophil serine proteases (NSPs) and fulminant periodontal inflammation of unknown cause. Here we investigated neutrophil extracellular trap (NET)-associated aggregation and cytokine/chemokine-release/degradation by normal and NSP-deficient human and mouse granulocytes. Stimulated with solid or soluble NET inducers, normal neutrophils formed aggregates and both released and degraded cytokines/chemokines. With increasing cell density, proteolytic degradation outweighed release. Maximum output of cytokines/chemokines occurred mostly at densities between 2 × 107 and 4 × 107 neutrophils/cm3. Assessment of neutrophil density in vivo showed that these concentrations are surpassed during inflammation. Association with aggregated NETs conferred protection of neutrophil elastase against α1-antitrypsin. In contrast, eosinophils did not influence cytokine/chemokine concentrations. The proteolytic degradation of inflammatory mediators seen in NETs was abrogated in Papillon-Lefèvre syndrome (PLS) neutrophils. In summary, neutrophil-driven proteolysis of inflammatory mediators works as a built-in safeguard for inflammation. The absence of this negative feedback mechanism might be responsible for the nonresolving periodontitis seen in PLS.-Hahn, J., Schauer, C., Czegley, C., Kling, L., Petru, L., Schmid, B., Weidner, D., Reinwald, C., Biermann, M. H. C., Blunder, S., Ernst, J., Lesner, A., Bäuerle, T., Palmisano, R., Christiansen, S., Herrmann, M., Bozec, A., Gruber, R., Schett, G., Hoffmann, M. H. Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases.

Authors with CRIS profile

Jonas Hahn Department of Medicine 3 – Rheumatology and Immunology Benjamin Schmid Optical Imaging Center Erlangen (OICE) Christiane Reinwald Department of Medicine 3 – Rheumatology and Immunology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Ralf Palmisano Optical Imaging Center Erlangen (OICE) Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Aline Bozec Juniorprofessur für Osteoimmunologie Georg Schett Lehrstuhl für Innere Medizin III Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

University of Cambridge GB United Kingdom (GB) Helmholtz-Zentrum Berlin für Materialien und Energie (HZB) DE Germany (DE) University of Gdańsk / Uniwersytet Gdański PL Poland (PL) Fraunhofer-Institut für Integrierte Systeme und Bauelementetechnologie (IISB) DE Germany (DE)

How to cite

APA:

Hahn, J., Schauer, C., Czegley, C., Kling, L., Petru, L., Schmid, B.,... Hoffmann, M. (2018). Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases. The FASEB Journal. https://dx.doi.org/10.1096/fj.201800752R

MLA:

Hahn, Jonas, et al. "Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases." The FASEB Journal (2018).

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