The role of human mast cell tryptase in allergic inflammation
The role of human mast cell tryptase in allergic inflammation
Mast cell tryptase, a tetrameric serine proteinase, is the major secretory product of human mast cells. We have investigated the potential contribution of this enzyme in allergic inflammation employing in vivo and in vitro models with laboratory animals and human tissues.
The injection of tryptase into the skin of guinea pigs induced microvascular leakage with a potency similar on a weight basis to that of histamine at lower doses. The reaction was dependent on an intact catalytic site, being inhibited by co-injecting tryptase with proteinase inhibitors or by heat-treating the enzyme. Tryptase-induced microvascular leakage was markedly reduced by pretreating animals with a combination of H1 and H2 histamine antagonists, suggesting that the actions of tryptase on the microvasculature may be mediated in part through the release of endogenous histamine. Consistent with this was our findings that tryptase was able to induce histamine release from dispersed guinea pig skin and lung mast cells in vitro, by a non-cytotoxic mechanism. By six hours following injection of tryptase into guinea pig skin, there was an accumulation of neutrophils and eosinophils at the injection site with some evidence of eosinophil degranulation. In parallel studies, intraperitoneal injection of tryptase in mice stimulated a massive influx of neutrophils and eosinophils, and there appeared to be increased recruitment also of lymphocytes and macrophages. In both models the actions of tryptase could be inhibited with proteinase inhibitors and by heat treating the enzyme. Coinjection of heparin with tryptase did not have consistent effects on accumulation of the various cell types. Histamine on the other hand, although it did not by itself stimulate an inflammatory cell influx, was able to enhance to a striking degree the eosinophil accumulation induced by tryptase, and to a less extent, tryptase-induced lymphocyte recruitment.
University of Southampton
He, Shaoheng
eed00fb6-a70a-4013-8b77-7273292d84b4
1996
He, Shaoheng
eed00fb6-a70a-4013-8b77-7273292d84b4
He, Shaoheng
(1996)
The role of human mast cell tryptase in allergic inflammation.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Mast cell tryptase, a tetrameric serine proteinase, is the major secretory product of human mast cells. We have investigated the potential contribution of this enzyme in allergic inflammation employing in vivo and in vitro models with laboratory animals and human tissues.
The injection of tryptase into the skin of guinea pigs induced microvascular leakage with a potency similar on a weight basis to that of histamine at lower doses. The reaction was dependent on an intact catalytic site, being inhibited by co-injecting tryptase with proteinase inhibitors or by heat-treating the enzyme. Tryptase-induced microvascular leakage was markedly reduced by pretreating animals with a combination of H1 and H2 histamine antagonists, suggesting that the actions of tryptase on the microvasculature may be mediated in part through the release of endogenous histamine. Consistent with this was our findings that tryptase was able to induce histamine release from dispersed guinea pig skin and lung mast cells in vitro, by a non-cytotoxic mechanism. By six hours following injection of tryptase into guinea pig skin, there was an accumulation of neutrophils and eosinophils at the injection site with some evidence of eosinophil degranulation. In parallel studies, intraperitoneal injection of tryptase in mice stimulated a massive influx of neutrophils and eosinophils, and there appeared to be increased recruitment also of lymphocytes and macrophages. In both models the actions of tryptase could be inhibited with proteinase inhibitors and by heat treating the enzyme. Coinjection of heparin with tryptase did not have consistent effects on accumulation of the various cell types. Histamine on the other hand, although it did not by itself stimulate an inflammatory cell influx, was able to enhance to a striking degree the eosinophil accumulation induced by tryptase, and to a less extent, tryptase-induced lymphocyte recruitment.
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Published date: 1996
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Local EPrints ID: 462949
URI: http://eprints.soton.ac.uk/id/eprint/462949
PURE UUID: 42711577-6204-4844-9fb2-fa82d9883608
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Date deposited: 04 Jul 2022 20:30
Last modified: 04 Jul 2022 20:30
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Author:
Shaoheng He
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