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Erschienen in: Inflammation Research 10/2020

06.07.2020 | Original Research Paper

A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice

verfasst von: Aline Dias de Almeida, Irismara Sousa Silva, Weslley Fernandes-Braga, Antônio Carlos Melo LimaFilho, R odrigo Machado Florentino, Ayslan Barra, Luciana de Oliveira Andrade, M. Fátima Leite, Geovanni Dantas Cassali, André Klein

Erschienen in: Inflammation Research | Ausgabe 10/2020

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Abstract

Objective

This study aims to investigate the role of protease-activated receptor (PAR) 2 and mast cell (MC) tryptase in LPS-induced lung inflammation and neutrophil recruitment in the lungs of C57BL/6 mice.

Methods

C57BL/6 mice were pretreated with the PAR2 antagonist ENMD-1068, compound 48/80 or aprotinin prior to intranasal instillation of MC tryptase or LPS. Blood leukocytes, C-X-C motif chemokine ligand (CXCL) 1 production leukocytes recovered from bronchoalveolar lavage fluid (BALF), and histopathological analysis of the lung were evaluated 4 h later. Furthermore, we performed experiments to determine intracellular calcium signaling in RAW 264.7 cells stimulated with LPS in the presence or absence of a protease inhibitor cocktail or ENMD-1068 and evaluated PAR2 expression in the lungs of LPS-treated mice.

Results

Pharmacological blockade of PAR2 or inhibition of proteases reduced neutrophils recovered in BALF and LPS-induced calcium signaling. PAR2 blockade impaired LPS-induced lung inflammation, PAR2 expression in the lung and CXCL1 release in BALF, and increased circulating blood neutrophils. Intranasal instillation of MC tryptase increased the number of neutrophils recovered in BALF, and MC depletion with compound 48/80 impaired LPS-induced neutrophil migration.

Conclusion

Our study provides, for the first time, evidence of a pivotal role for MCs and MC tryptase in neutrophil migration, lung inflammation and macrophage activation triggered by LPS, by a mechanism dependent on PAR2 activation.
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Metadaten
Titel
A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice
verfasst von
Aline Dias de Almeida
Irismara Sousa Silva
Weslley Fernandes-Braga
Antônio Carlos Melo LimaFilho
R odrigo Machado Florentino
Ayslan Barra
Luciana de Oliveira Andrade
M. Fátima Leite
Geovanni Dantas Cassali
André Klein
Publikationsdatum
06.07.2020
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 10/2020
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-020-01376-4

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