Alpha tryptase: Potential roles in inflammation distinct from those of b-tryptase
Alpha tryptase: Potential roles in inflammation distinct from those of b-tryptase
RATIONALE: Tryptases are among the most abundant products of the humanmast cell. Beta-tryptase has emerged as an important mediator of allergicinflammation. The copy number of a-tryptase has recently beenfound to be associated with the asthma phenotype, but the function ofthis allelic variant to b-tryptase is unknown.We have investigated potentialactions of a-tryptase.
METHODS: C57BL/6 mice were injected intra-peritoneally with recombinanta or b-tryptases (0.005 or 0.5 ug/mouse; 12 mice per group). After6, 12 or 24 h, mice were killed and peritoneal lavage performed.Inflammatory cells were enumerated and levels of albumin and total proteindetermined. Gelatine zymography was applied to examine the activityof matrix metalloprotease (MMP)-2 and MMP-9. In separate experiments,cells of the human bronchial epithelial line 16HBE were incubated withtryptases and expression of mRNA for IL-8, IL-6 and TNF-a examinedby quantitative PCR.
RESULTS: Injection of a-tryptase induced the accumulation of neutrophils,eosinophils, macrophages and mast cells (p<0.01) but not lymphocytes.Under the same conditions, b-tryptase stimulated greaterneutrophil recruitment, but the accumulation of other cell types was lessmarked. MMP-9 activity in lavage fluid was unaffected in a-tryptase injectedmice, but it was increased in those injected with b-tryptase.Following addition of a-tryptase to epithelial cells, there was down-regulationof mRNA for IL-6 and TNF-a (p<0.05) whereas b-tryptase inducedstrong up-regulation of the cytokines investigated.
CONCLUSION: Recombinant a-tryptase may be a stimulus for the recruitmentof inflammatory cells and altered cytokine gene expressionwith effects different from those of b-tryptase.
Khedr, M.E.M.S.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Abdelmotelb, Ahmed
cebf8ef6-9dbe-433d-b8ac-f9f8c0ee3f94
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sommerhoff, Christian P.
c69636c3-04ba-44b2-9153-a391df1c559c
1 February 2010
Khedr, M.E.M.S.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Abdelmotelb, Ahmed
cebf8ef6-9dbe-433d-b8ac-f9f8c0ee3f94
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sommerhoff, Christian P.
c69636c3-04ba-44b2-9153-a391df1c559c
Khedr, M.E.M.S., Abdelmotelb, Ahmed, Pender, Sylvia, Walls, Andrew, Zhou, Xiaoying, Holloway, John and Sommerhoff, Christian P.
(2010)
Alpha tryptase: Potential roles in inflammation distinct from those of b-tryptase.
Journal of Allergy and Clinical Immunology, 125 (2, Supplement 1), [AB178].
(doi:10.1016/j.jaci.2009.12.696).
Record type:
Meeting abstract
Abstract
RATIONALE: Tryptases are among the most abundant products of the humanmast cell. Beta-tryptase has emerged as an important mediator of allergicinflammation. The copy number of a-tryptase has recently beenfound to be associated with the asthma phenotype, but the function ofthis allelic variant to b-tryptase is unknown.We have investigated potentialactions of a-tryptase.
METHODS: C57BL/6 mice were injected intra-peritoneally with recombinanta or b-tryptases (0.005 or 0.5 ug/mouse; 12 mice per group). After6, 12 or 24 h, mice were killed and peritoneal lavage performed.Inflammatory cells were enumerated and levels of albumin and total proteindetermined. Gelatine zymography was applied to examine the activityof matrix metalloprotease (MMP)-2 and MMP-9. In separate experiments,cells of the human bronchial epithelial line 16HBE were incubated withtryptases and expression of mRNA for IL-8, IL-6 and TNF-a examinedby quantitative PCR.
RESULTS: Injection of a-tryptase induced the accumulation of neutrophils,eosinophils, macrophages and mast cells (p<0.01) but not lymphocytes.Under the same conditions, b-tryptase stimulated greaterneutrophil recruitment, but the accumulation of other cell types was lessmarked. MMP-9 activity in lavage fluid was unaffected in a-tryptase injectedmice, but it was increased in those injected with b-tryptase.Following addition of a-tryptase to epithelial cells, there was down-regulationof mRNA for IL-6 and TNF-a (p<0.05) whereas b-tryptase inducedstrong up-regulation of the cytokines investigated.
CONCLUSION: Recombinant a-tryptase may be a stimulus for the recruitmentof inflammatory cells and altered cytokine gene expressionwith effects different from those of b-tryptase.
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Published date: 1 February 2010
Additional Information:
Program and abstracts of papers to be presented during Scientific sessions: 2010 AAAAI Annual Meeting
Venue - Dates:
American Academy of Allergy, Asthma & Immunology (AAAAI), , New Orleans, United States, 2010-02-25 - 2010-03-01
Identifiers
Local EPrints ID: 432852
URI: http://eprints.soton.ac.uk/id/eprint/432852
ISSN: 0091-6749
PURE UUID: b289d918-2e2d-4a01-a15f-7ddc814ed4ff
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Date deposited: 31 Jul 2019 16:30
Last modified: 17 Mar 2024 02:45
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Author:
M.E.M.S. Khedr
Author:
Ahmed Abdelmotelb
Author:
Xiaoying Zhou
Author:
Christian P. Sommerhoff
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