Mast cells in chronic rejection of human renal allografts

An increased number of mast cells (MCs) is found in renal specimens of pati ents with diseases associated with persistent chronic inflammation. MCs pro liferation is partly dependent on the presence of T lymphocytes. Both chron ic inflammation and T-lymphocytes are essential in the development of chron ic rejection (CR), and probably for the infiltration of MCs. MC-derived pro ducts such as heparin, histamine, and serine proteases may be responsible f or endothelial proliferation and excess collagen production by fibroblasts. In this study, a quantitative evaluation of the MCs infiltration in kidney allografts with CR is performed. The extent of renal. fibrosis was analyse d in samples stained with Masson's trichrome. To evaluate the potential rel ationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtaine d from patients died by causes not related with rejection were used as cont rols. CR was graded according to the Banff schema, which assesses the degre e of vasculopathy, tubular atrophy, interstitial fibrosis and transplantati on glomerulopathy. Giemsa-stained sections and immunohistochemistry using a nti-MG tryptase and c-kit monoclonal antibodies were used to detect MCs. Th e mean number of MCs per 20 high-power fields (HPF) in the transplanted kid ney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the me dulla. MCs were significantly more numerous in CR with respect to normal ki dneys, both in the cortex (P<0.01; Mann-Whitney U test) and in the medulla (P<0.01; Mann-Whitney U test). There was a positive correlation between the number of MCs and extent of fibrosis (P<0.01; Kruskal-Wallis one-way anova test) and tubular atrophy (P<0.01). These results suggest that MCs may pla y a role in the process of development of interstitial fibrosis in CR.