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Title: The regulation of mast cell growth and protease expression by cytokines
Author: Newlands, George Frederick James
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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In this study the diversity of mast cell proteases and some of the factors regulating mast cell growth and protease expression were examined in rodents. Five proteases were isolated from mouse small intestinal mucosa and their substrate specificities defined. The isolated proteases were all of mast cell origin and were chymotrypsin-like in their substrate specificities. The proteases were all identified as variants of mouse mast cell protease-1 which differed only in their carbohydrate moieties. Despite the fact that these enzymes shared a common core polypeptide they all differed significantly in the rate at which they hydrolysed synthetic substrates and in the rates at which they were inhibited by α1-proteinase inhibitor. A related, but distinct protease was isolated from peritoneal cavity mast cells of mice. This enzyme, also a chymase, had N-terminal sequence identity with mouse mast cell protease-4. This enzyme was not inhibited by α1-proteinase inhibitor. Factors which regulate mast cell survival, growth, proliferation and protease expression were examined in the rat. Stem cell factor (SCF) or cytokine-rich lymph node-conditioned medium (LNCM) was administered to normal rats by intraperitoneal injection and the effects on the connective tissue mast cells (CTMC) of the peritoneal cavity were monitored. LNCM did not cause in increase in CTMC numbers but it did stimulate a switch in protease expression from rat mast cell protease 1 (RMCP I) alone to dual expression of both RMCP I and II. SCF alone caused a significant increase in CTMC numbers coupled with a decrease in RMCP I content, and an increase in RMCP II content/cell. Treatment with both LNCM and SCF together caused an even greater increase in both CTMC numbers and RMCP II expression than with SCF alone. Daily intravenous injection for SCF for 14 days into both normal and Nippostrongylus brasiliensis-infected rats resulted in a five-fold increase in CTMC numbers with a concomitant decrease in RMCP I content. There was no significant expression of RMCP II in the CTMC of these animals. These results show that SCF and the cytokines in LNCM play an important role in the regulation of mast cell populations and their expression of proteases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available