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).
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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- Faculties (pre 2018 reorg) > Faculty of Engineering and the Environment (pre 2018 reorg) > Southampton Marine & Maritime Institute (pre 2018 reorg)
- Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Clinical & Experimental Sciences (pre 2018 reorg)
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Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg) - Faculties (pre 2011 reorg) > Faculty of Medicine Health & Life Sciences (pre 2011 reorg) > Medicine (pre 2011 reorg)
Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Medicine (pre 2011 reorg) - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Institute for Life Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg)
Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine
- Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences
Clinical and Experimental Sciences
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