Stem cell factor and crescentic glomerulonephritis.
BACKGROUND
Numerous cells and cytokines have been implicated in the pathogenesis of crescentic glomerulonephritis (CGN). Recently, there has been growing awareness of the role of mast cells and their growth factor, stem cell factor (SCF), in the process of tissue inflammation and fibrosis.


METHODS
In this study, renal biopsy specimens from 28 patients with a histopathologic diagnosis of CGN were evaluated immunohistochemically for the presence of mast cells, SCF, and its receptor (c-kit). In addition, CD34+ hematopoietic cells, monocytes (CD68+ cells), and myofibroblasts (alpha-smooth muscle actin-positive [alpha-SMA+] cells) were counted. Renal biopsy specimens from cadaveric kidney donors and kidneys removed for hypernephroma (n = 6) served as controls. Point counting of positive immunostaining for SCF, alpha-SMA, and collagens III and IV was undertaken. Glomerular and interstitial fibrosis (IF) scores were determined.


RESULTS
Patients who developed progressive chronic kidney failure showed a significant increase in percentage of crescents, number of interstitial c-kit+ cells, and glomerular CD68+ cells compared with those with a favorable outcome. Analysis showed a significant elevation of tryptase+ mast cells in the interstitium of renal biopsy specimens of patients with CGN compared with controls. SCF and c-kit+ cells were found in glomeruli and interstitium, with occasional immunostaining of the crescent with SCF. Both glomerular and interstitial SCF immunostaining was significantly higher in biopsy specimens of patients compared with controls. Glomerular and interstitial SCF showed a significant positive correlation with 24-hour urinary protein level. There were a few CD34+ cells in both glomeruli and interstitium, but their numbers did not differ between patients and controls. Colocalization of CD34+ and c-kit+ was seen in some rounded interstitial and spindle-shaped cells. Number of interstitial mast cells proved to be a strong predictor of IF. Glomerular SCF correlated negatively with creatinine clearance and positively with glomerular CD68+ cells. Interstitial immunostainable SCF correlated positively with interstitial CD68+ cells and interstitial collagen III. On double antigen labeling, SCF was shown in the vicinity of alpha-SMA+ cells.


CONCLUSIONS
These results show the potential involvement of mast cells and their growth factor SCF/c-kit in CGN.
El Kossi
Mohsen M H
MM
Sheffield Kidney Institute, University of Sheffield, Sheffield, UK.
El Nahas
A Meguid
AM
D000199:Actins / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D002452:Cell Count; D024061:Collagen Type III / Q000032:analysis; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000502:physiology*; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000502:physiology*; D012697:Serine Endopeptidases / Q000032:analysis; D019089:Stem Cell Factor / Q000032:analysis / Q000502:physiology*; D053802:Tryptases; D015854:Up-Regulation; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D024061:Collagen Type III; D003404:Creatinine; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; D019089:Stem Cell Factor; D053802:Tryptases; C067980:CD68 antigen, human; D000097382:CD68 Molecule