The development of a novel immunoassay for the quantification of active tryptase

Ferguson, Timothy; McCafferty, Darragh; Robb, Charlene; Moffitt, Kelly; Walker, Brian

doi:10.1183/1393003.congress-2017.pa4017

Cited by 1 publication

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“…The unique tetrameric architecture of β-tryptases affords the ability of this enzyme to undertake biochemical and biological roles that deviate from those typical of trypsin and most other TLPs [ 19 , 20 ]. Mast cell tryptase has been implicated as the driving force behind a range of chronic airway inflammation and remodelling processes, such as airway smooth muscle and epithelial cell hyperplasia and angiogenesis, with involvement in the development of allergic asthma and the pathogenesis of COPD [ 19 , 21 ]. Conformational restrictions, resulting from the small size of the enzyme active site, help explain why tryptase is notoriously resistant to proteinaceous inactivators of TLPs such as aprotinin [ 22 ].…”

Section: Serine Trypsin-like Proteases (Tlps)mentioning

confidence: 99%

Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases

Carroll

Bailo

Reihill

et al. 2021

IJMS

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Trypsin-like proteases (TLPs) belong to a family of serine enzymes with primary substrate specificities for the basic residues, lysine and arginine, in the P1 position. Whilst initially perceived as soluble enzymes that are extracellularly secreted, a number of novel TLPs that are anchored in the cell membrane have since been discovered. Muco-obstructive lung diseases (MucOLDs) are characterised by the accumulation of hyper-concentrated mucus in the small airways, leading to persistent inflammation, infection and dysregulated protease activity. Although neutrophilic serine proteases, particularly neutrophil elastase, have been implicated in the propagation of inflammation and local tissue destruction, it is likely that the serine TLPs also contribute to various disease-relevant processes given the roles that a number of these enzymes play in the activation of both the epithelial sodium channel (ENaC) and protease-activated receptor 2 (PAR2). More recently, significant attention has focused on the activation of viruses such as SARS-CoV-2 by host TLPs. The purpose of this review was to highlight key TLPs linked to the activation of ENaC and PAR2 and their association with airway dehydration and inflammatory signalling pathways, respectively. The role of TLPs in viral infectivity will also be discussed in the context of the inhibition of TLP activities and the potential of these proteases as therapeutic targets.

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