Mast cells mediate the severity of experimental cystitis in mice.
OBJECTIVE
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.


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.
Bjorling
D E
DE
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA.
Jerde
T J
TJ
Zine
M J
MJ
Busser
B W
BW
Saban
M R
MR
Saban
R
R
D000818:Animals; D003556:Cystitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D012720:Severity of Illness Index; D013373:Substance P / Q000494:pharmacology
D008070:Lipopolysaccharides; D013373:Substance P