Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis.
BACKGROUND
Mast cells have never been extensively investigated in renal disease, particularly glomerulonephritis. Recent improvements in monoclonal antibody production to mast cell specific enzymes have made it possible to study mast cells in tissues more accurately and easily. Mast cells have been found to secrete basic fibroblast growth factor (bFGF) in human pulmonary fibrosis.


METHODS
Mast cells in 67 cases of IgA nephritis were investigated. Toluidine blue (TB) stainings at pH 5.0 and pH 0.5 were employed histochemically, and anti-human mast cell tryptase and chymase monoclonal antibodies were used immunohistochemically. Anti-bFGF antibody was also used immunohistochemically.


RESULTS
Mast cells were scattered in the interstitium including in fibrotic areas. TB pH 0.5-positive mast cells were more numerous than TB pH 5. 0-positive mast cells. Immunostaining with anti-tryptase monoclonal antibody detected more mast cells than the TB stainings. Mast cells in the interstitium of IgA nephritis had both tryptase and chymase. Immunoelectron microscopy showed that tryptase was exclusively localized in the specific granules of mast cells. The average number of tryptase positive mast cell in the interstitium of IgA nephritis was lower than that of T lymphocyte but more than that of macrophages. The average number of mast cells increased with the progression of interstitial fibrosis and had a significant correlation with 24-hour creatinine clearance. Using double labeled immunohistochemistry, some tryptase-positive mast cells had bFGF in their cytoplasm. Electron microscopy showed that mast cells were associated with fibroblasts and/or lymphocytes in the interstitium.


CONCLUSIONS
Mast cells are one of the constitutive cells in the interstitium of IgA nephritis patients and affect renal function by contributing to the interstitial fibrosis.
Ehara
T
T
First Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan. ehara@sch.md.shinshu-u.ac.jp
Shigematsu
H
H
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D053818:Chymases; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology* / Q000648:ultrastructure; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism; D014048:Tolonium Chloride; D053802:Tryptases
D014048:Tolonium Chloride; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases