INTRAGRANULAR ACTIVATION OF BLADDER MAST-CELLS AND THEIR ASSOCIATION WITH NERVE PROCESSES IN INTERSTITIAL CYSTITIS

Objective To investigate the presence of progesterone receptors and th e extent and type of degranulation exhibited by the increased numbers of mast cells (MCs) found in interstitial cystitis (IC), a painful bla dder disorder which occurs almost exclusively in women, worsens perime nstrually and is characterized by increased numbers of oestradiol rece ptor (OR)-positive MCs. Patients and methods The state of MC degranula tion was analysed blindly using electron microscopy of bladder biopsie s from 26 patients with IC and six control patients which included fiv e women with incontinence, with none of the established characteristic s of IC, and one man with transitional carcinoma of the bladder. Empha sis was placed on preserving the secretory granule ultrastructure. The presence of progesterone receptors (PRs) in five patients with IC and three controls was investigated using commercially available antibodi es against PRs. Results Over 85% of bladder MCs expressed high affinit y PRs, but the number of PR-positive MCs in patients with IC did not d iffer significantly from that of controls despite the overall increase in MCs seen in IC. MCs were activated to various degrees and were oft en near to neuronal processes, The secretory granule content of MCs fr om patients with IC was in different stages of dissolution, ranging fr om heterogeneous loss of electron density to the appearance of crystal line substructure and target forms containing only remnants of the ori ginal material. Typical degranulation by compound exocytosis was not o bserved. MCs from control patients contained secretory granules with m ostly intact, electron-dense granules. Conclusion These findings indic ate that the symptoms of IC may depend on an imbalance of the relative number of oestrogen receptors (ORs) to PRs on bladder MCs resulting i n a 'progesterone deficient' state. This possibility is strengthened b y demonstration that oestradiol augments the secretion of MC histamine in response to the neuropeptide substance P, which is pro-inflammator y nociceptive and overexpressed in bladders with IC. Intragranular act ivation of bladder MCs is a characteristic pathological finding in pat ients with IC. The lack of extensive degranulation, typically seen in anaphylaxis, may indicate a unique mode of stimulation and/or differen tial release of mediators.