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Mast cells and anti-inflammatory drugs: studies of mediator release and calcium mobilization.

by Grant Richardson Stenton. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 259-287). / Abstract --- p.i / Acknowledgements --- p.iii / Publications --- p.iv / Abbreviations --- p.v / Contents --- p.vii / Chapter Chapter 1 --- Introduction / Chapter 1 1.1. --- Historical Background --- p.2 / Chapter 1.2. --- Origin and distribution of mast cells --- p.2 / Chapter 1.3. --- Mast cell heterogeneity --- p.3 / Chapter 1.4. --- Mast cell mediators --- p.5 / Chapter 1.4.1. --- Preformed mast cell mediators --- p.6 / Chapter 1.4.2. --- Newly synthesised mast cell mediators --- p.7 / Chapter 1.5. --- Mast cell activation --- p.11 / Chapter 1.5.1. --- Antigenic pathway of mast cell activation --- p.11 / Chapter 1.5.1.1. --- Antigen binding and receptor aggregation --- p.12 / Chapter 1.5.1.2. --- Early events following FcεRI aggregation --- p.13 / Chapter 1.5.1.3. --- Antigenic induction of mast cell second messenger production --- p.15 / Chapter 1.5.1.4. --- Phospholipase C activation and mast cells --- p.16 / Chapter 1.5.1.5. --- Phospholipase A2 activation and mast cells --- p.17 / Chapter 1.5.1.6. --- Intracellular calcium and mast cells --- p.18 / Chapter 1.5.1.7. --- Calcium and calmodulin --- p.21 / Chapter 1.5.1.8. --- Adenylate cyclase activation and mast cells --- p.21 / Chapter 1.5.2. --- Non-antigenic pathway of mast cell activation --- p.22 / Chapter 1.6. --- Aims of the study --- p.25 / Chapter 1.6.1. --- Diuretics --- p.26 / Chapter 1.6.2. --- Histamine receptor directed compounds --- p.27 / Chapter 1.6.3. --- Cyclo-oxygenase inhibitors --- p.28 / Chapter 1.6.4. --- Immunosuppressive compounds --- p.29 / Chapter Chapter 2 --- Materials and Methods --- p.31 / Chapter 2.1. --- Materials and methods --- p.32 / Chapter 2.1.1. --- Secretagogues --- p.32 / Chapter 2.1.2. --- Anti-allergic compounds --- p.32 / Chapter 2.1.3. --- Diuretics --- p.32 / Chapter 2.1.4. --- Immunosuppressants --- p.33 / Chapter 2.1.5. --- Histamine agonists and antagonists --- p.33 / Chapter 2.1.6. --- Cyclo-oxygenase inhibitors --- p.33 / Chapter 2.1.7. --- Materials for buffers --- p.34 / Chapter 2.1.8. --- Materials for rat sensitization --- p.34 / Chapter 2.1.9. --- Materials for histamine assay --- p.35 / Chapter 2.1.10. --- Materials for calcium measurement --- p.35 / Chapter 2.1.11. --- Materials for prostaglandin D2 measurement --- p.35 / Chapter 2.1.12. --- Materials for leukotriene C4 measurement --- p.36 / Chapter 2.1.13. --- Materials for cyclic AMP measurement --- p.36 / Chapter 2.1.14. --- Miscellaneous --- p.36 / Chapter 2.2. --- Buffers and stock solutions --- p.37 / Chapter 2.2.1. --- Buffer ingredients --- p.37 / Chapter 2.2.2. --- Stock solutions --- p.38 / Chapter 2.3. --- Animals and cell isolation --- p.39 / Chapter 2.3.1. --- Animals --- p.39 / Chapter 2.3.2. --- Sensitization of animals --- p.39 / Chapter 2.3.3. --- Cell isolation --- p.40 / Chapter 2.3.4. --- Cell washing and purification --- p.41 / Chapter 2.3.5. --- Preparation of cells for counting --- p.42 / Chapter 2.3.6. --- Cell counting on a haemocytometer --- p.42 / Chapter 2.4. --- General protocol for histamine release and histamine measurement --- p.43 / Chapter 2.4.1. --- Histamine release --- p.43 / Chapter 2.4.2. --- Spectroflurometric determination of histamine contents --- p.44 / Chapter 2.4.3. --- Calculation of histamine levels --- p.45 / Chapter 2.5. --- Protocol for cellular calcium measurement --- p.47 / Chapter 2.5.1. --- 45Ca2+ influx measurement --- p.47 / Chapter 2.5.2. --- Calculation of 45Ca2+ influx --- p.48 / Chapter 2.5.3. --- Fura-2 fluorescence measurement of intracellular calcium --- p.48 / Chapter 2.5.4. --- Fura-2 cell loading --- p.48 / Chapter 2.5.5. --- Fura-2 fluorescence parameters --- p.49 / Chapter 2.5.6. --- Calculation of basal calcium levels --- p.50 / Chapter 2.6. --- Protocol for prostaglandin D2 (PGD2) measurement --- p.52 / Chapter 2.6.1. --- PGD2 production --- p.52 / Chapter 2.6.2. --- Enzyme Immunosorbent Assay (EIA) method of PGD2 measurement --- p.52 / Chapter 2.6.3. --- Calculation of (EIA) PGD2 production --- p.53 / Chapter 2.6.4. --- Radio Immunosorbent Assay (RIA) method of PGD2 measurement --- p.53 / Chapter 2.6.5. --- Calculation of (RIA) PGD2 concentration --- p.54 / Chapter 2.7. --- Protocol for leukotriene C4 (LTC4) measurement --- p.54 / Chapter 2.7.1. --- LTC4 production --- p.54 / Chapter 2.7.2. --- Enzyme Immunosorbent Assay (EIA) method of LTC4 measurement --- p.55 / Chapter 2.7.3. --- Calculation of (EIA) LTC4 concentration --- p.55 / Chapter 2.8. --- Protocol for cyclic adenosine monophosphate (cAMP) measurement --- p.56 / Chapter 2.8.1. --- cAMP production --- p.56 / Chapter 2.8.2. --- Radio Immunosorbent Assay (RIA) method of cAMP measurement --- p.56 / Chapter 2.8.3. --- Calculation of cAMP concentration --- p.57 / Chapter 2.9. --- Statistical analysis --- p.57 / Chapter Chapter 3 --- "Frusemide, Bumetanide and DSCG" --- p.58 / Chapter 3.1. --- Introduction --- p.59 / Chapter 3.1.1. --- Frusemide and bumetanide as loop diuretics --- p.59 / Chapter 3.1.2. --- Effects of frusemide and bumetanide on the airways --- p.59 / Chapter 3.1.3. --- Effects of frusemide on mast cells --- p.60 / Chapter 3.1.4. --- Experimental aims --- p.61 / Chapter 3.2. --- Materials and methods --- p.62 / Chapter 3.3. --- Results --- p.63 / Chapter 3.3.1 --- "Effects of frusemide, bumetanide and DSCG on immunologically induced histamine release from rat peritoneal mast cells" --- p.63 / Chapter 3.3.2. --- "Effects of frusemide, bumetanide and DSCG on compound 48/80 induced histamine release from rat peritoneal mast cells" --- p.64 / Chapter 3.3.3. --- "Effects of frusemide, bumetanide and DSCG on compound 48/80 induced histamine release from rat peritoneal mast cells suspended in calcium free buffer" --- p.65 / Chapter 3.3.4. --- "Effects of frusemide, bumetanide and DSCG on ionophore A23187 and thapsigargin induced histamine release from rat peritoneal mast cells" --- p.65 / Chapter 3.3.5. --- Cross-tachyphylaxis effects of frusemide and bumetanide --- p.66 / Chapter 3.3.6. --- Effects of DSCG on the inhibition of anaphylactic histamine release due to frusemide --- p.67 / Chapter 3.3.7. --- Effects of frusemide and DSCG on immunologically and non-immunologically induced 45Ca2+ uptake --- p.67 / Chapter 3.3.8. --- Effects of frusemide and DSCG on immunologically and non-immunologically induced changes in the free intracellular calcium concentration of rat peritoneal mast cells --- p.68 / Chapter 3.3.9. --- Effects of frusemide and bumetanide on the spontaneous and secretagogue induced PGD2 production from rat peritoneal mast cells --- p.69 / Chapter 3.3.10. --- Effects of frusemide and DSCG on cellular cAMP levels --- p.70 / Chapter 3.4. --- Discussion --- p.101 / Chapter 3.5. --- Summary --- p.111 / Chapter 3.6. --- Conclusion --- p.114 / Chapter 3.7. --- Future studies --- p.114 / Chapter Chapter 4 --- Histamine Receptor Directed Compounds --- p.115 / Chapter 4.1. --- Introduction --- p.116 / Chapter 4.1.1. --- Histamine receptor subtypes --- p.116 / Chapter 4.1.2. --- Histamine effects on the airways --- p.117 / Chapter 4.2. --- Signal transduction mechanisms --- p.118 / Chapter 4.2.1. --- H1-receptors --- p.118 / Chapter 4.2.2. --- H2-receptors --- p.119 / Chapter 4.2.3. --- H3-receptors --- p.120 / Chapter 4.3. --- Histamine receptors and mast cells --- p.120 / Chapter 4.3.1. --- Effects of histamine agonists and antagonists on mast cells --- p.120 / Chapter 4.3.2. --- Experimental aims --- p.122 / Chapter 4.3.3. --- Materials and methods --- p.123 / Chapter 4.4. --- Results --- p.123 / Chapter 4.4.1. --- Effects of the test compounds on the spontaneous histamine release from rat peritoneal mast cells --- p.123 / Chapter 4.4.2. --- Effects of the test compounds on anti-IgE induced histamine release from rat peritoneal mast cells --- p.125 / Chapter 4.4.3. --- Effects of the test compounds on compound 48/80 induced histamine release from rat peritoneal mast cells --- p.126 / Chapter 4.4.4. --- Effects of the test compounds on anti-IgE and compound 48/80induced histamine release from rat peritoneal mast cells in calcium free buffer --- p.126 / Chapter 4.4.5. --- Effects of the test compounds on ionophore A23187 induced histamine release from rat peritoneal mast cells --- p.127 / Chapter 4.4.6. --- "Effects of histamine antagonists on dimaprit, imetit and impromidine induced histamine release from rat peritoneal mast cells" --- p.128 / Chapter 4.4.7. --- "Effects of anti-IgE, dimaprit and imetit on PGD2 production from rat peritoneal mast cells" --- p.128 / Chapter 4.4.8. --- "Effects of benzalkonium chloride (BAC) on dimaprit, imetit, compound 48/80 and anti-IgE induced histamine release from rat peritoneal mast cells" --- p.129 / Chapter 4.4.9. --- "Effects of pertussis toxin on dimaprit, imetit, compound 48/80and anti-IgE induced histamine release from rat peritoneal mast cells" --- p.129 / Chapter 4.4.10. --- "Effects of dimaprit, imetit, compound 48/80 and anti-IgE on the free intracellular calcium concentration of rat peritoneal mast cells" --- p.130 / Chapter 4.5. --- Discussion --- p.171 / Chapter 4.5.1. --- The possible existence of histamine receptors on rat peritoneal mast cells --- p.171 / Chapter 4.5.2. --- "Possible mechanism of action for the histamine releasing actions of dimaprit, imetit and impromidine on rat peritoneal mast cells" --- p.174 / Chapter 4.6. --- Conclusion --- p.181 / Chapter 4.7. --- Future studies --- p.182 / Chapter Chapter 5 --- Cyclo-oxygenase Inhibitors --- p.184 / Chapter 5.1. --- Introduction --- p.185 / Chapter 5.1.1. --- Cyclo-oxygenase isozymes --- p.185 / Chapter 5.1.2. --- Cyclo-oxygenase inhibitors and mast cells --- p.186 / Chapter 5.1.3. --- Experimental aims --- p.190 / Chapter 5.2. --- Materials and methods --- p.190 / Chapter 5.3. --- Results --- p.191 / Chapter 5.3.1. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced histamine release from rat peritoneal mast cells - --- p.191 / Chapter 5.3.2. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced PGD2 production from rat peritoneal mast cells --- p.192 / Chapter 5.3.3. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced LTC4 production from rat peritoneal mast cells --- p.192 / Chapter 5.3.4. --- Effects of cyclo-oxygenase inhibitors on immunologically and non-immunologically induced 45Ca uptake by rat peritoneal mast cells --- p.193 / Chapter 5.4. --- Discussion --- p.221 / Chapter 5.5. --- Summary and Conclusion --- p.225 / Chapter Chapter 6 --- Immunosuppressive Drugs --- p.228 / Chapter 6.1. --- Introduction --- p.229 / Chapter 6.1.1. --- CsA and FK506 binding proteins --- p.230 / Chapter 6.1.2. --- Distribution of CyPA and FKBP12 --- p.231 / Chapter 6.1.3 --- Mechanism of immunosuppression --- p.232 / Chapter 6.1.4. --- The role of calcineurin in IL-2 promoter induction --- p.233 / Chapter 6.2. --- Immunosuppressive agents and mast cells --- p.234 / Chapter 6.2.1. --- Introduction --- p.234 / Chapter 6.2.2. --- CsA and FK506 inhibit mast cell cytokine production --- p.235 / Chapter 6.2.3. --- "CsA mediated inhibition of mediator release from, and calcium uptake by mast cells and basophils" --- p.236 / Chapter 6.2.4. --- Inhibition of mediator release from mast cells and basophils by FK506 --- p.239 / Chapter 6.2.5. --- Aim of this study --- p.240 / Chapter 6.2.6. --- Materials and methods --- p.241 / Chapter 6.3. --- Results --- p.241 / Chapter 6.3.1. --- Effects of CsA and FK506 on immunologically and non-immunologically induced histamine release from rat peritoneal mast cells --- p.241 / Chapter 6.3.2. --- Effects of CsA and FK506 on immunologically and non-immunologically induced PGD2 production from rat peritoneal mast cells --- p.242 / Chapter 6.3.3. --- Effects of CsA and FK506 on immunologically and non-immunologically induced 45Ca uptake by rat peritoneal mast cells --- p.243 / Chapter 6.4. --- Discussion --- p.254 / Chapter 6.4.1. --- "Effects of CsA on histamine release from, and 45Ca uptake by rat peritoneal mast cells, following immunological and non-immunological activation" --- p.254 / Chapter 6.4.2. --- Effects of CsA on PGD2 production from rat peritoneal mast cells --- p.256 / Chapter 6.4.3. --- "Effects of FK506 on histamine release from, and 45Ca uptake by rat peritoneal mast cells, following immunological and non-immunological activation" --- p.256 / Chapter 6.4.4. --- Effects of FK506 on immunological PGD2 production from rat peritoneal mast cells --- p.257 / Chapter 6.5. --- Summary --- p.257' / Chapter 6.6. --- Future work --- p.258 / References

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_321693
Date January 1996
ContributorsStenton, Grant Richardson., Chinese University of Hong Kong Graduate School. Division of Basic Medical Sciences.
PublisherChinese University of Hong Kong
Source SetsThe Chinese University of Hong Kong
LanguageEnglish
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xii, 287 leaves : ill. ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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