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

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

Research output: Contribution to journalArticle

Abstract

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 smokeinduced 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.

Original languageEnglish (US)
Pages (from-to)18214-18227
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number26
DOIs
StatePublished - Jun 27 2014

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Tryptases
Pulmonary diseases
Serine Proteases
Colitis
Mast Cells
Chronic Obstructive Pulmonary Disease
Lung
Peptide Hydrolases
Membranes
IgE Receptors
Dextran Sulfate
Methacholine Chloride
Calcium Ionophores
Homologous Recombination
Alveolar Macrophages
Cell membranes
Inbred C57BL Mouse
Tobacco Products
Interleukin-6
Colon

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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

In: Journal of Biological Chemistry, Vol. 289, No. 26, 27.06.2014, p. 18214-18227.

Research output: Contribution to journalArticle

Hansbro, PM, Hamilton, MJ, Fricker, M, Gellatly, SL, Jarnicki, AG, Zheng, D, Frei, SM, Wong, GW, Hamadi, S, Zhou, S, Foster, PS, Krilis, SA & Stevens, RL 2014, 'Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis', Journal of Biological Chemistry, vol. 289, no. 26, pp. 18214-18227. https://doi.org/10.1074/jbc.M114.548594
Hansbro, Philip M. ; Hamilton, Matthew J. ; Fricker, Michael ; Gellatly, Shaan L. ; Jarnicki, Andrew G. ; Zheng, Dominick ; Frei, Sandra M. ; Wong, Guang William ; Hamadi, Sahar ; Zhou, Saijun ; Foster, Paul S. ; Krilis, Steven A. ; Stevens, Richard L. / Importance of mast cell Prss31/transmembrane tryptase/tryptase-γ in lung function and experimental chronic obstructive pulmonary disease and colitis. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 26. pp. 18214-18227.
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AU - Jarnicki, Andrew G.

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AU - Frei, Sandra M.

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