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Mast cells mediate the severity of experimental cystitis in mice
D E Bjorling1, T J Jerde, M J Zine
1Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA.
Purpose:
We hypothesized that experimental cystitis induced by substance P (SP) or E. coli lipopolysaccharide (LPS) would be less severe in mice rendered mast cell deficient by genetic manipulation.
Materials And Methods:
Two strains of mast-cell deficient mice (WBB6F1- kitW/kitW-v or kitW/kitW-v and WCB6F1-Sl/Sld or Sl/Sld) and their congenic, normal (+/+) counterparts were used. Cystitis was induced in female mice by intravenous injection of SP (0.1 ml.; 10(-6) M) or E. coli LPS (0.1 ml.; 2 mg./ml.), and inflammation was assessed by Evans blue dye extravasation. In a separate group of kitW/kitW-v and congenic normal mice, cystitis was induced by intravesical infusion of SP (0.05 ml.; 10(-5) M) or E. coli LPS (0.05 ml.; 100 microg./ml.) and compared with intravesical pyrogen-free saline (0.05 ml.; 0.9%). Severity of cystitis was determined by histological evaluation of the bladder wall 24 hours after intravesical infusions.
Results:
Intravenous SP or LPS stimulated increased plasma extravasation in congenic normal mice but not in mast cell-deficient mice. Intravesical SP or LPS resulted in increased edema, leukocytic infiltration, and hemorrhage within the bladder wall in congenic normal mice, but the only histological evidence of inflammation in the bladders of kitW/kitW-v mice was increased hemorrhage in response to LPS.
Conclusions:
This study indicates that mast cells modulate the inflammatory response of the bladder to SP and LPS in mice. Although clinical trials of the use of antihistamines to treat or prevent cystitis have not been successful, these results suggest that therapies directed toward preventing mast cell activation may yet prove effective in treating cystitis.
Insights
Mast cells play a key role in bladder inflammation caused by substance P (SP) and lipopolysaccharide (LPS). Targeting mast cell activation may offer new treatments for cystitis.
Area of Science:
- Immunology
- Urology
Background:
- Mast cells are immune cells involved in inflammatory responses.
- Cystitis is a common bladder inflammation with various causes.
- Substance P (SP) and E. coli lipopolysaccharide (LPS) are known to induce experimental cystitis.
Purpose of the Study:
- To investigate the role of mast cells in experimental cystitis induced by SP or LPS.
- To determine if mast cell deficiency reduces the severity of cystitis.
Main Methods:
- Used mast cell-deficient mice (WBB6F1-kitW/kitW-v and WCB6F1-Sl/Sld) and their normal counterparts.
- Induced cystitis via intravenous or intravesical administration of SP or LPS.
- Assessed inflammation by measuring plasma extravasation (Evans blue dye) and histological evaluation of bladder tissue.
Main Results:
- Mast cell-deficient mice showed significantly reduced inflammation compared to normal mice after SP or LPS challenge.
- Intravenous SP or LPS increased plasma extravasation in normal mice, but not in mast cell-deficient mice.
- Intravesical SP or LPS induced edema, leukocytic infiltration, and hemorrhage in normal mice, while mast cell-deficient mice only showed increased hemorrhage with LPS.
Conclusions:
- Mast cells are critical modulators of the inflammatory response in the bladder to SP and LPS.
- Therapies targeting mast cell activation may be a promising approach for treating cystitis.
- This study provides a basis for developing novel anti-inflammatory strategies for bladder conditions.