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The roles of beta and alpha tryptases in asthma: genetic and immunopharmacological studies

The roles of beta and alpha tryptases in asthma: genetic and immunopharmacological studies
The roles of beta and alpha tryptases in asthma: genetic and immunopharmacological studies
Tryptases, the dominant secretory granular proteins from human mast cells, are emerging as important mediators in asthma and allergy. The β- and α- tryptases have highly similar nucleotide sequences and located on the same locus. While the entire population expresses β-tryptase, the α-tryptase gene exhibits copy number variation (CNV). We have studied the association of expression of these allelic variants with asthma or allergic diseases. We have investigated also the potential actions of β- and α-tryptases in vitro and in vivo. We have found that the one alpha tryptase copy allele was significantly associated with lower total serum IgE levels (Z= -2.39, p=0.01) and a tri-allelic architecture with alleles carrying no, one or two copies of the α-tryptase gene was postulated. The addition of βtryptase to epithelial cells induced upregulation of mRNA for IL-8, IL-6 and TNF-α, while α-tryptase on the other hand was without effect in this model. Injection of β-tryptase into the mouse peritoneum induced great accumulation of neutrophils but accumulation of other cell types was less marked. Under the same conditions, injection of α- tryptase induced less neutrophilia but eosinophils, macrophages and mast cells numbers were significantly increased. The actions of β-tryptase seemed be independent of PAR-2 receptors but not the case for α-tryptase, where PAR-2 pathway might take the leads. In conclusion, recombinant α-tryptase may be a stimulus for the recruitment of inflammatory cells and altered cytokine gene expression with effects distinct from those of β-tryptase.
University of Southampton
Abdelmotelb, Ahmed Asem Mahrous
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Abdelmotelb, Ahmed Asem Mahrous
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe

Abdelmotelb, Ahmed Asem Mahrous (2010) The roles of beta and alpha tryptases in asthma: genetic and immunopharmacological studies. University of Southampton, Doctoral Thesis, 177pp.

Record type: Thesis (Doctoral)

Abstract

Tryptases, the dominant secretory granular proteins from human mast cells, are emerging as important mediators in asthma and allergy. The β- and α- tryptases have highly similar nucleotide sequences and located on the same locus. While the entire population expresses β-tryptase, the α-tryptase gene exhibits copy number variation (CNV). We have studied the association of expression of these allelic variants with asthma or allergic diseases. We have investigated also the potential actions of β- and α-tryptases in vitro and in vivo. We have found that the one alpha tryptase copy allele was significantly associated with lower total serum IgE levels (Z= -2.39, p=0.01) and a tri-allelic architecture with alleles carrying no, one or two copies of the α-tryptase gene was postulated. The addition of βtryptase to epithelial cells induced upregulation of mRNA for IL-8, IL-6 and TNF-α, while α-tryptase on the other hand was without effect in this model. Injection of β-tryptase into the mouse peritoneum induced great accumulation of neutrophils but accumulation of other cell types was less marked. Under the same conditions, injection of α- tryptase induced less neutrophilia but eosinophils, macrophages and mast cells numbers were significantly increased. The actions of β-tryptase seemed be independent of PAR-2 receptors but not the case for α-tryptase, where PAR-2 pathway might take the leads. In conclusion, recombinant α-tryptase may be a stimulus for the recruitment of inflammatory cells and altered cytokine gene expression with effects distinct from those of β-tryptase.

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AAM ABDELMOTEL PhD thesis - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: April 2010

Identifiers

Local EPrints ID: 434582
URI: http://eprints.soton.ac.uk/id/eprint/434582
PURE UUID: 10df8809-f2df-4a41-bd61-692d08a4faf5

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Date deposited: 02 Oct 2019 16:30
Last modified: 02 Oct 2019 16:30

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