International Neurourology Journal 2011;15:61-63 Potential Targeting of Siglecs, Mast Cell Inhibitory Receptors, in Interstitial Cystitis Chang-Shin Park1,2, Bruce S. Bochner3 1Department of Pharmacology, Inha University School of Medicine, Incheon; 2Medicinal Toxicology Research Center, Inha Institute of Research for Medical Sciences, and Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project, Inha University School of Medicine, Incheon, Korea 3Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

International Neurourology Journal 2011;15:61-63 Interstitial cystitis (IC) is a chronic bladder inflammatory disease that is characterized by symptoms such as urinary urgency, frequency, nocturia, and suprapubic and pelvic pain and that mainly affect women. Although the exact etiology and pathogenesis of IC is unknown, one etiologic theory that has been dominantly reported in relation to the bladder immune is that of a localized allergic reaction. Both clinical and experimental evidence show that IC is closely associated with an accumulation of mast cells and their activation, especially in the detrusor, lamina propria, and submucosa. Recently, detrusor mast cell migration and activation and urinary histamine metabolites have been detected in IC patients and in experimentally induced animal models.

International Neurourology Journal 2011;15:61-63 As a result, the UPs are synthesized in large quantities only by terminally differentiated urothelial cells. For this reason, the UPs can be regarded as a major urothelial differentiation marker. UP II ablation completely abolishes plaque formation and contain abnormal epithelial polyps or complete epithelial occlusion in their ureters. UP IIIa ablasion is also associated with impairment of the urothelial permeability barrier and development of vesicoureteral reflux as well as a decrease in urothelial plaque size. In this review, published studies about UPs and attempt to explain the clinical significance of our laboratory results are summerized.

International Neurourology Journal 2011;15:61-63 Mast cells are well known to be involved in both acute and chronic forms of allergic, type I hypersensitivity reactions. After activation, a characteristic pattern of mast cell mediators is released during degranulation. These include preformed granule-associated inflammatory mediators (e.g., histamine, heparin, neutral proteases, proteoglycans, glycoprotein-like YKL-40, chemotactic substances, and cytokines such as TNF-α), newly synthesized mediators (e.g., prostaglandin D2 [PGD2], leukotriene B4 and C4, interleukin-6 [IL-6], platelet- activating factor, and nitric oxide), and potent vasodilatory mediators (e.g., vasoactive intestinal peptide). These mast cell-released mediators are implicated in causing IC bladder pathophysiology.

International Neurourology Journal 2011;15:61-63 Mast cell survival and activation, which are mediated mainly by phosphorylation signals, can be negatively regulated by engaging the inhibitory receptors (IRs) containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). A classic form of several IRs on human mast cells is FcγRIIB, which can down-regulate mast cell activation when co-ligated with high-affinity IgE receptor (FcεRI). Mast cells also express one or more ITIM sequence-containing IRs, such as sialic acid-binding immunoglobulin- like lectins (Siglecs), on the cell surface to regulate their inflammatory or allergic activation. We introduce the potential application of Siglec antibodies to the mast cells to activate Siglec IRs in the inflammatory urinary bladder disease IC.