Mast Cells in Rapidly Progressive Glomerulonephritis

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Abstract
The role of mast cells (MC) in tubulointerstitial damage in glomerulonephritis (GN) is not fully understood. The distribution of MC was compared in renal biopsies from 50 patients with different stages of rapidly progressive GN (RPGN) and in 20 control samples. The immunoreactivity of renal MC with anti-tryptase and anti-chymase antibodies was studied. Interstitial myofibroblasts were stained with anti-α-smooth muscle actin (α-SMA) antibody, and inflammatory cells were identified by anti-CD3, -CD20, and -CD68 monoclonal antibodies. Positively stained cells were counted, and the relative interstitial and fractional areas of anti-α-SMA-stained cells were measured. MC were rarely found in control samples. In contrast, samples showing crescentic GN contained numerous tryptase-positive MC (MCT) (43.7 ± 4.65 versus 7.14 ± 1.3/mm2) and fewer tryptase- and chymase-positive MC (MCTC) (13.8 ± 1.86 versus 1.89 ± 0.86/mm2) in the renal interstitium but never in the glomerulus. Double immunostaining demonstrated the presence of both phenotypes of MC. Accumulation of MC was significantly correlated with the numbers of T lymphocytes (MCT, r = 0.67) and interstitial macrophages (MCT, r = 0.455). There was also a significant correlation between the number of MCT and the relative interstitial area. The number of MCTC was well correlated with the fractional area of α-SMA-positive interstitium (r = 0.749) and the percentage of the interstitial fibrotic area (r = 0.598). There was also a significant negative correlation between interstitial MCTC accumulation and creatinine clearance (r = 0.661). The density of MCTC was higher (1.4-fold) in advanced forms of GN associated with fibrocellular crescents and interstitial fibrosis. These results show the potential involvement of MC in the fibroproliferative process in the renal interstitium of patients with RPGN. The results indicate that these cells constitute part of the overall inflammatory cell accumulation in RPGN.

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