Gibbs, Bernhard Frederick; (1995) Some studies on the release of cytokines and other mediators from mast cells of the rat and human. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Recent studies have suggested that mast cells are capable of producing and releasing a number of pro-inflammatory cytokines which can modify the function and proliferation of a variety of cell types. However, these studies have mainly been carried out using murine tissue culture derived mast cells and it is known that these cells differ markedly in their functional properties compared to isolated human mast cells. It was therefore essential to study the release of cytokines from the latter cell type. Human lung mast cells were recovered by enzymatic digestion of the intact tissue and purified to between 60 and 90 % homogeneity by density gradient centrifugation and counter current elutriation. These preparations were shown to contain basal levels of mRNA for tumour necrosis factor alpha (TNF-a). On immunologic activation, the cells rapidly released, within 2-10 min, small amounts of TNF-a and interleukins 4 and 6 (IL-4 and IL-6). After longer periods of activation (0.5 - 4 h), the amounts of cytokines decreased. These changes and the amounts of cytokines produced were unaffected by the addition of protease inhibitors. In addition, the effects of purification and changes in environment on rat and human lung mast cells were investigated. Purification of both cell types led to a decrease in responsivity to various stimuli and to an increased sensitivity to anti-allergic drugs. These changes in responsiveness were partially reversed by the addition of supernatants from incubated non mast cell fractions which are usually discarded during the purification processes. Additionally, catabolism of histamine was observed following the addition of supernatants from non mast cell rich human lung fractions. These studies also showed that the spontaneous histamine secretion of isolated mast cells may be altered by the densities of isolated cells. Environmental conditions may therefore play a crucial role in regulating the reactivity and properties of mast cells. Finally, the effects of anti-allergic drugs on rat and human mast cells were compared and the effect of a novel herbal extract used in the treatment of eczema was studied.

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