Frenz,, Anne Maria; (1995) Some studies on the mast cell of the bladder and skin from the human and other species. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

In this study, the functional characteristics of the bladder and the skin mast cells of the mouse, rat, guinea pig and human have been examined. Of particular interest was the functional heterogeneity displayed m vitro by different tissue mast cells to a range of secretagogues and the inhibition of anti-IgE induced histamine release by various therapeutic anti-allergic agents. It has long been recognised that mast cells play an important role in the pathogenesis and aetiology of the chronic inflammatory bladder disease intersritial cystitis (IC). Human bladder mast cells isolated from macroscopical normal tissue obtained from cancer patients and patients suffering from IC were functionally compared and it was shown that mast cells from the diseased tissue were generally more responsive towards immunological stimuli. This increase in sensitivity was also seen when the mast cells were exposed to ionophore A23187. In contrast, substance P (SP) and compound 48/80 were shown to be more effective towards normal muscle mast cells than IC muscle mast cells. Previous results were confirmed in that only mast cells from human bladder and skin released histamine in response to SP and compound 48/80, whilst lung mast cells are unresponsive. Mast cells isolated from the readily available muscle cf IC bladder were also tested for prostaglandin D2 (PGD2) and tryptase release. It was found that the bladder mast cells released PGD2 and tryptase in response to anti- IgE and ionophore A23187 but not SP and compound 48/80. Bladder biopsies examined under an electron microscope provided further evidence that mast cells in the detrusor muscle may play a crucial role ir the pathogenesis of IC. Despite considerable and sustained attempts to repeat previous work on human skin mast cells, it has not been possible to obtain substantial histamine release with anti-human IgE. Throughout the studies, simple 10 min incubation of mast cells with anti-human IgE caused a maximal histamine release of 5%. However, incubation of mast cells with stem cell factor (SCF) induced potentiation of anti- IgE stimulated release. SCF is primarily a product of fibroblasts and has been found to be critical in mast cell development. It may well prove to be one of the most important factors influencing mast cell numbers, phenotype, and function in both health and disease. Parathyroid hormone (PTH) is an important regulator of bone turnover. In addition, the biologically active fragment (1-34) of human parathyroid hormone (1-34 hPTH) has also been reported to induce mediator release from rat serosal and peritoneal mast cells and thus been implicated as a potential contributor to the regulation of bone and cartilage metabolism. Elevated mast cell numbers have been observed in the bone marrows of patients with postmenopausal osteoporosis. In this study, 1-34 hPTH was found to release histamine only at maximal concentrations (20 μM) from rat peritoneal mast cells. However, lower concentrations of 1-34 hPTH did potentiate anti-IgE mediated histamine release from rat mast cells. 1-34 hPTH did not induce or potentiate anti-IgE mediated histamine release from human lung mast cells or human basophils. More recently, herbal medicine has received much media attention for the treatment of skin allergies such as eczema, urticaria and atopic dermatitis, where conventional medicine seems to have failed. Here we have compared ten components of a herbal extract now commonly administered to skin-allergy patients on rat peritoneal mast cells and found that three active anti-allergic components inhibited histamine release from cells stimulated with anti-rat IgE. In conclusion, the present study has provided more understanding of the extent and nature of mast cell heterogeneity, with special reference to the role of mast cells in different disease processes.

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