Mast cells in chronic rejection of human renal allografts.
An increased number of mast cells (MCs) is found in renal specimens of patients with diseases associated with persistent chronic inflammation. MCs proliferation is partly dependent on the presence of T lymphocytes. Both chronic inflammation and T-lymphocytes are essential in the development of chronic rejection (CR), and probably for the infiltration of MCs. MC-derived products such as heparin, histamine, and serine proteases may be responsible for 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 analysed in samples stained with Masson's trichrome. To evaluate the potential relationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtained from patients died by causes not related with rejection were used as controls. CR was graded according to the Banff schema, which assesses the degree of vasculopathy, tubular atrophy, interstitial fibrosis and transplantation glomerulopathy. Giemsa-stained sections and immunohistochemistry using anti-MC tryptase and c-kit monoclonal antibodies were used to detect MCs. The mean number of MCs per 20 high-power fields (HPF) in the transplanted kidney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the medulla. MCs were significantly more numerous in CR with respect to normal kidneys, 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 play a role in the process of development of interstitial fibrosis in CR.
Pardo
J
J
Department of Pathology, Clínica Universitaria, University of Navarra, Pamplona, Spain. jpardo@unav.es
Diaz
L
L
Errasti
P
P
Idoate
M
M
de Alava
E
E
Sola
I
I
Lozano
L
L
Panizo
A
A
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002648:Child; D002908:Chronic Disease; D053818:Chymases; D005355:Fibrosis; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014184:Transplantation, Homologous; D053802:Tryptases
D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases