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Updated: Oct 23, 2025
Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction
Goutham Pattabiraman1, Ashlee J Bell-Cohn1, Stephen F Murphy1
1Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Abstract:
Intraurethral inoculation of mice with uropathogenic Escherichia coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of a mast cell stabilizer, cromolyn sodium, and the histamine 1 receptor antagonist cetirizine di-hydrochloride in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW & NOTEWORTHY LUTS-associated benign prostatic hyperplasia is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model, suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.
Insights
Mast cells drive prostate inflammation and urinary dysfunction in a mouse model of benign prostatic hyperplasia (BPH). Inhibiting mast cells reduced symptoms and reversed prostate pathology, suggesting a new therapeutic target for BPH and lower urinary tract symptoms (LUTS).
Area of Science:
- Urology
- Immunology
- Pathophysiology
Background:
- Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) involve prostate inflammation, fibrosis, and smooth muscle contraction.
- Mast cells are implicated in LUTS pathophysiology, but their precise role requires further elucidation.
- Uropathogenic *Escherichia coli* (CP1) infection in mice models key aspects of BPH/LUTS.
Purpose of the Study:
- To investigate the role of mast cells in the pathophysiology of CP1-induced prostate inflammation and urinary dysfunction.
- To evaluate the therapeutic potential of mast cell inhibition for BPH/LUTS.
Main Methods:
- Intraurethral inoculation of mice with uropathogenic *Escherichia coli* (CP1).
- Therapeutic intervention using a combination of cromolyn sodium (mast cell stabilizer) and cetirizine di-hydrochloride (histamine 1 receptor antagonist).
- Assessment of prostate pathology, immune cell infiltration, fibrosis, inflammation, and urinary function.
- Measurement of myosin light chain-2 phosphorylation as a marker of smooth muscle contraction.
Main Results:
- CP1 infection induced prostate inflammation, fibrosis, mast cell activation, and urinary dysfunction in mice.
- Mast cell inhibition significantly alleviated urinary dysfunction and reduced prostate inflammation, fibrosis, and immune cell infiltration.
- Treated mice exhibited reduced myosin light chain-2 phosphorylation, indicating decreased smooth muscle contraction.
Conclusions:
- Mast cells play a critical role in the pathophysiology of urinary dysfunction associated with BPH/LUTS.
- Therapeutic inhibition of mast cells effectively alleviates prostate pathology and urinary symptoms in a mouse model.
- Mast cell inhibition represents a promising therapeutic strategy for preventing and reversing BPH/LUTS pathology and symptoms.
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