28 research outputs found
Chronic pelvic allodynia is mediated by CCL2 through mast cells in an experimental autoimmune cystitis model
The cause of chronic pelvic pain in interstitial cystitis/painful bladder syndrome (IC/PBS) remains unclear; autoimmunity is a possible etiology. We have recently shown that injection of a single immunogenic peptide of uroplakin 3A (UPK3A 65-84) induces experimental autoimmune cystitis (EAC) in female BALB/cJ mice that is unique among experimental models in accurately reflecting both the urinary symptoms and pelvic pain of IC/PBS. The aim of this project was to identify the roles of mast cells and mast cell chemoattractant/activator monocyte chemoattractant protein-1 [chemokine (C-C motif) ligand 2 (CCL2)] in the allodynia in this model. We immunized 6- to 8-wk-old female BALB/cJ mice with UPK3A 65-84 peptide and, 5-40 days later, observed increased responses to stimulation of the suprapubic abdominal and hindpaw surfaces with von Frey monofilaments compared with mice injected with adjuvant alone. Suprapubic and hindpaw tactile allodynia responses by EAC mice were blocked by instillation of lidocaine into the bladder but not by lidocaine in the uterus, confirming the bladder as the source of the hypersensitivity. Markedly increased numbers of activated mast cells and expression of CCL2 were found in the bladder after immunization with UPK3A 65-84. Hypersensitive responses were inhibited by mast cell stabilizer cromolyn sodium and antagonists of histamine receptors 1 and 2. Furthermore, BALB/cJ mice with deletion of the Ccl2 or chemokine (C-C motif) receptor 2 gene exhibited markedly reduced allodynia and accumulation of mast cells after UPK3A 65-84 immunization. These results show that UPK3A 65-84 immunization causes chronic visceral allodynia and suggest that it is mediated by CCL2-driven mast cell accumulation in the bladder
Autoimmunity to Uroplakin II Causes Cystitis in Mice: A Novel Model of Interstitial Cystitis
Background: The pathophysiology of interstitial cystitis (IC) is unknown. Deficits in urothelial cell layers and autoimmune mechanisms may play a role
Additional file 2: Figure S2. of Classification of follicular lymphoma: the effect of computer aid on pathologists grading
Graphical User Interface of the proposed FLAGS system. (DOCX 1052 kb
Additional file 1: Figure S1. of Classification of follicular lymphoma: the effect of computer aid on pathologists grading
Flow of the detection process: (a) H&E image, (b) CD20 image, (c) S channel of H&E, (d) S channel of CD20, (e) Registered CD20 (S channel), (f) Local thresholding with blocks showing detected HPF regions, (g) Detected HPFs on CD20 (S channel), (h) Detected HPFs on the H&E. (DOCX 384 kb
Additional file 5: Figure S5. of Classification of follicular lymphoma: the effect of computer aid on pathologists grading
Reader-Specific ROC Curves. Readers 1-4 were expert hematopathologists. Readers 5-11 were residents. (DOCX 21 kb