The role of neutrophil elastase in elastin metabolism of pelvic tissues from women with stress urinary incontinence.
OBJECTIVE
Altered elastin metabolism is implicated in pelvic floor disorders. We studied neutrophil elastase (NE) and matrix metalloproteinase (MMP) activities in vaginal tissues from premenopausal women with stress urinary incontinence (SUI).


METHODS
Elastase and NE activities in vaginal tissues were assessed. Protein and mRNA expressions were determined by RT-PCR and Western blot. Total elastin and collagen contents were evaluated. To compare the relative elastolytic effect of NE and MMP-2, we used their respective antibodies to immunoprecipitate these proteins from vaginal fibroblast extracts prior to assessing elastase activity.


RESULTS
Elastase activity in vaginal wall tissues was significantly higher in the secretory compared to the proliferative phase. NE mRNA and protein expressions were similar between control and SUI tissues from the secretory phase. However, NE activity in the SUI tissues was higher compared to control tissues. The mRNA expression of alpha-1 antitrypsin (ATT) was higher in control tissues from the proliferative phase compared to those from the secretory phase, while no difference was observed in SUI tissues between either phase. Protein expression of the active form of ATT was decreased in SUI tissues compared to controls during the secretory phase. Anti-NE antibody reduced total elastase activity by 60-70%, compared to less than 20% reduction with anti-MMP-2 antibody.


CONCLUSIONS
During the secretory phase, elastolytic activity is increased in pelvic tissues from women with SUI, through an increase in NE activity and a concurrent decrease in ATT expression. The serine protease, NE, appears to be a more significant modulator of elastase activity compared to MMP-2.
Chen
Bertha
B
Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. bchen@stanford.edu
Wen
Yan
Y
Yu
Xiaoyun
X
Polan
Mary Lake
ML
D000328:Adult; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014550:Urinary Incontinence, Stress / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D012065:Relaxin; D003094:Collagen; D004549:Elastin; D019272:Leukocyte Elastase; D020782:Matrix Metalloproteinases