Extracellular matrix degradation and reduced nerve supply in refluxing ureteral endings.
OBJECTIVE
Extracellular matrix (ECM) degrading enzymes and the nerve supply of the ureterovesical junction were investigated using immunohistochemical methods to gain insight into the pattern of refluxing ureteral endings.


METHODS
Specimens were obtained from ureterorenal units of 36 children undergoing reflux surgery with a mean age of 62.5 months and 9 age matched controls without reflux. Routine histological paraffin embedded sections were stained for general morphology. Indirect immunohistochemical methods assessing matrix metalloproteinase 1 were used to study the intensity of matrix turnover, and activated macrophage marker CD68 was quantified to describe scavenging of damaged ECM. The intramural neuronal network was explored using nerve specific immunoperoxidase for S-100 protein.


RESULTS
Refluxing ureteral endings demonstrated structural deficiencies of the smooth muscle wrap associated with a 3.8-fold increase of cellular matrix metalloproteinase 1 production and a significant increase of CD68+ macrophages, respectively. The S-100 pattern yielded significant diminution. Lacking B and T lymphocytes in the ECM precluded chronic inflammation.


CONCLUSIONS
Refluxing ureteral endings showed a pathologically increased matrix remodeling combined with deprivation of the intramural nerve supply. Macrophage activation referring to altered morphology was represented by an increased expression of CD68 at the sites of increased ECM turnover.
Department of Pediatric Urology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Josef
J
Oswald
Christian
C
Schwentner
Erich
E
Brenner
Martina
M
Deibl
Helga
H
Fritsch
Georg
G
Bartsch
Christian
C
Radmayr
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D009130:Muscle, Smooth / Q000737:chemistry / Q000294:innervation; D009415:Nerve Net / Q000473:pathology; D009418:S100 Proteins / Q000032:analysis; D014513:Ureter / Q000737:chemistry / Q000294:innervation* / Q000473:pathology*; D014718:Vesico-Ureteral Reflux / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D020781:Matrix Metalloproteinase 1; D009418:S100 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule