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

Journal article


Publication Details

Author(s): 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
Journal: The FASEB Journal
Publication year: 2018
ISSN: 0892-6638
eISSN: 1530-6860


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.


FAU Authors / FAU Editors

Bäuerle, Tobias Prof. Dr.
Professur für Multimodale Bildgebung in der präklinischen Forschung
Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Hahn, Jonas
Medizinische Klinik 3 - Rheumatologie und Immunologie
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Medizinische Klinik 3 - Rheumatologie und Immunologie
Palmisano, Ralf Dr.
Optical Imaging Center Erlangen (OICE)
Reinwald, Christiane
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Schmid, Benjamin Dr.
Optical Imaging Center Erlangen (OICE)


External institutions with authors

Fraunhofer-Institut für Integrierte Systeme und Bauelementetechnologie (IISB)
Helmholtz-Zentrum Berlin für Materialien und Energie (HZB)
University of Cambridge
University of Gdańsk / Uniwersytet Gdański


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).

BibTeX: 

Last updated on 2019-10-09 at 09:33