Neutrophils from allergic asthmatic patients produce and release metalloproteinase-9 upon direct exposure to allergens

Ventura, I., Vega, A., Chacon Fernandez, Pedro, Chamorro, C., Aroca, R., Gómez, E., Bellido, V., Puente, Y., Blanca, M. and Monteseirín, J. 2014. Neutrophils from allergic asthmatic patients produce and release metalloproteinase-9 upon direct exposure to allergens. Allergy 69 (7) , pp. 898-905. 10.1111/all.12414

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Abstract

Background Asthma is characterized by airway inflammation and remodelling in which matrix metalloproteinases (MMPs) play an important role. MMP-9 is the major MMP found in the bronchoalveolar lavage fluids and bronchial biopsies from patients with allergic asthma after allergen challenge, where it correlates with the count of neutrophils and macrophages. However, the cellular sources of MMP-9 in this inflammatory condition have not yet been clearly identified. This work was undertaken to analyse whether neutrophils may be a source of MMP-9 in the allergic asthma condition upon allergen challenge. Methods Neutrophils from allergic asthmatic patients were in vitro stimulated, and the levels of MMP-9 release were measured in the cell culture supernatants using enzyme-linked immunosorbent assay (ELISA) and zymography. Results We show that MMP-9 is released by neutrophils, but not by eosinophils from allergic asthmatic patients in response to allergens to which the patients were sensitized. Neutrophils also released MMP-9 in response to anti-IgE Abs, and agonist Abs against FcεRI, FcεRII/CD23 and galectin-3. Inhibitors of transcription and translation, actinomycin D and cycloheximide, partially cancelled this process, suggesting that MMP-9 is also de novo synthesized in response to stimuli. We also show evidence that the MAPKs, p38 and extracellular signal-regulated kinase, as well as the transcription factor NF-κB, are involved, as specific chemical inhibitors of these cell-signalling pathways abolished the anti-IgE/allergen-dependent MMP-9 release. Conclusions These data demonstrate that the exposure of neutrophils to allergens leads to generation of MMP-9, which may then lead to remodelling in asthma.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QR Microbiology
Uncontrolled Keywords:	allergen; asthma; IgE; metalloproteinase-9; neutrophils
Publisher:	Wiley-Blackwell
ISSN:	0105-4538
Last Modified:	28 Jun 2019 02:01
URI:	https://orca.cardiff.ac.uk/id/eprint/65862

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