Increased expression of mast cells in reflux nephropathy.
End-stage renal disease is characterized by interstitial infiltrate of inflammatory cells in association with tubular atrophy and interstitial fibrosis. Mast cells (MCs) secrete a large number of fibrogenic factors and have been implicated in chronic inflammatory processes with fibrous tissue deposition. The aim of this study was to investigate the distribution of MCs in kidneys with reflux nephropathy (RN) and to determine the relationship between MCs and the interstitial fibrotic process in RN. Kidney specimens from 12 patients (aged 2-13 years) with severe RN secondary to primary high-grade vesicoureteral reflux, obtained at the time of nephrectomy, and 5 controls were examined. Sections were investigated histochemically by acid toluidine blue (TB) and immunohistochemically with antibodies for anti MC-tryptase, MC-chymase, c- kit (CD117), and fibronectin. Double staining for fibronectin and MC-tryptase was performed and examined using confocal scanning microscopy. TB histochemistry showed a marked increase of MCs in RN specimens compared with controls. MC-tryptase, chymase, and c- kit immunopositive MC infiltration was significantly higher in RN samples (14.2+/-9.6) than controls (1.3+/-0.8), ( P<0.05). In all the sections there were more MC-tryptase-positive cells than MC-chymase-positive MCs. Double staining showed increased immunoreactivity of MCs and fibrosis in the renal interstitium of kidneys with RN. The number of infiltrating tryptase-positive MCs was correlated with the degree of interstitial renal scarring. This study demonstrates for the first time the increased expression of MCs in RN, suggesting that MCs may be involved in the development of scarring in RN.
Solari
Valeria
V
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
Unemoto
Kei
K
Piaseczna Piotrowska
Anna
A
Puri
Prem
P
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D053818:Chymases; D004396:Coloring Agents; D005355:Fibrosis; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008407:Mast Cells / Q000473:pathology*; D018613:Microscopy, Confocal; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014048:Tolonium Chloride; D053802:Tryptases; D014718:Vesico-Ureteral Reflux / Q000150:complications*
D004396:Coloring Agents; D014048:Tolonium Chloride; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; D053818:Chymases; D053802:Tryptases