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
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:69 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 69(2020), 10 vom: 06. Okt., Seite 1059-1070 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Almeida, Aline Dias [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.08.2021 Date Revised 04.08.2021 published: Print-Electronic ErratumIn: Inflamm Res. 2020 Aug 7;:. - PMID 32767096 Citation Status MEDLINE |
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| doi: |
10.1007/s00011-020-01376-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312101708 |
|---|
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| 100 | 1 | |a de Almeida, Aline Dias |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 04.08.2021 | ||
| 500 | |a Date Revised 04.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ErratumIn: Inflamm Res. 2020 Aug 7;:. - PMID 32767096 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a LPS-induced inflammation | |
| 650 | 4 | |a Lung inflammation | |
| 650 | 4 | |a Mast cell tryptase | |
| 650 | 4 | |a Neutrophil recruitment | |
| 650 | 4 | |a PAR2 | |
| 650 | 4 | |a Protease-activated receptor-2 | |
| 650 | 7 | |a 1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine |2 NLM | |
| 650 | 7 | |a Chemokine CXCL1 |2 NLM | |
| 650 | 7 | |a Cxcl1 protein, mouse |2 NLM | |
| 650 | 7 | |a F2rl1 protein, mouse |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Receptor, PAR-2 |2 NLM | |
| 650 | 7 | |a Tryptases |2 NLM | |
| 650 | 7 | |a EC 3.4.21.59 |2 NLM | |
| 700 | 1 | |a Silva, Irismara Sousa |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes-Braga, Weslley |e verfasserin |4 aut | |
| 700 | 1 | |a LimaFilho, Antônio Carlos Melo |e verfasserin |4 aut | |
| 700 | 1 | |a Florentino, R Odrigo Machado |e verfasserin |4 aut | |
| 700 | 1 | |a Barra, Ayslan |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira Andrade, Luciana |e verfasserin |4 aut | |
| 700 | 1 | |a Leite, M Fátima |e verfasserin |4 aut | |
| 700 | 1 | |a Cassali, Geovanni Dantas |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, André |e verfasserin |4 aut | |
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