Mast cells have been traditionally found at the interfaces with the body's exterior, such as the skin and the lungs. These cells degranulate in response to immunoglobulin E (IgE) and antigen (Ag) leading to increased secretion of inflammatory mediators in allergies, asthma, systemic mastocytosis and pruritus. More recently, mast cells have been shown to secrete in response to neuropeptides and to be in synaptic contact with neurons. Mast cells are also present in the gastrointestinal mucosa and increasing evidence indicates that they are plentiful in the bladder wall of patients with interstitial cystitis (I.C) where they may participate in the pathophysiology of this disease. However, no study to date has carefully examined the morphological and secretory characteristics of mast cells from active I.C. patients. Our multidisciplinary study will utilize clinical, cytological and biochemical methodologies to: (a) quantitate and characterize the types of mast cells in the bladder wall, (b) study the morphologic and ultrastructural characteristics of these mast cells and (c) evaluate their secretory capabilities by measuring their mediators in urine of I.C. patients and from biopsy samples used in special perfusion chambers. This latter approach will investigate the ability of acetylcholine (Ach), somatostatin (SRIF), substance P (SP), as well as human immunoglobulin E (IgE) and anti-IgE to induce secretion from human bladder mast cell in situ. Assays of secretion will involve measurement of bladder mast cell histamine, prostaglandin D2 (PGDs), leukotriene C4 (LTC4) and Beta- hexosaminidase, as well as interleukin I (IL-I) and Tamm-Horsfall glycoprotein (uromodulin). These mediators will measured both during secretion form fresh biopsy material in perfusion chambers, in bladder washing before surgery, and in 24 hour urine collection from I.C> patients. The effects of some inhibitors of mast cell pathophysiology in I.C., and may possibly facilitate new approaches to the prevention and treatment of I.C.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Tufts University
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Theoharides, Theoharis C; Whitmore, Kristine; Stanford, Edward et al. (2008) Interstitial cystitis: bladder pain and beyond. Expert Opin Pharmacother 9:2979-94
Theoharides, Theoharis C; Kempuraj, Duraisamy; Tagen, Michael et al. (2007) Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 217:65-78
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Vasiadi, M; Kempuraj, D; Boucher, W et al. (2006) Progesterone inhibits mast cell secretion. Int J Immunopathol Pharmacol 19:787-94
Theoharides, Theoharis C; Sant, Grannum R (2005) Immunomodulators for treatment of interstitial cystitis. Urology 65:633-8
Theoharides, Theoharis C; Bielory, Leonard (2004) Mast cells and mast cell mediators as targets of dietary supplements. Ann Allergy Asthma Immunol 93:S24-34
Theoharides, Theoharis C (2004) Panic disorder, interstitial cystitis, and mast cells. J Clin Psychopharmacol 24:361-4
Theoharides, Theoharis C; Cochrane, David E (2004) Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 146:1-12
Theoharides, T C; Kempuraj, D; Sant, G R (2001) Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology 57:47-55

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