Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis

Hansbro, Philip M.; Hamilton, Matthew J.; Foster, Paul S.; Krilis, Steven A.; Stevens, Richard L.; Fricker, Michael; Gellatly, Shaan L.; Jarnicki, Andrew G.; Zheng, Dominick; Frei, Sandra M.; Wong, G. William; Hamadi, Sahar; Zhou, Saijun

Title: Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis
Creator: Hansbro, Philip M.; Hamilton, Matthew J.; Foster, Paul S.; Krilis, Steven A.; Stevens, Richard L.; Fricker, Michael; Gellatly, Shaan L.; Jarnicki, Andrew G.; Zheng, Dominick; Frei, Sandra M.; Wong, G. William; Hamadi, Sahar; Zhou, Saijun
Relation: Journal of Biological Chemistry Vol. 289, Issue 26, p. 18214-18227
Publisher Link: http://dx.doi.org/10.1074/jbc.M114.548594
Publisher: American Society for Biochemistry and Molecular Biology
Resource Type: journal article
Date: 2014
Description: Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-γ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31^−/− C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases.
Subject: chronic obstructive pulmonary disease (COPD); inflammation; inflammatory bowel disease (IBD); mast cell; protease
Identifier: http://hdl.handle.net/1959.13/1302225
Identifier: uon:20434
Identifier: ISSN:0021-9258
Language: eng
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