Mast cell chymase expression and mast cell phenotypes in human rejected kidneys

Background. Mast cells (MCs) are known to participate in various types of c hronic disease, but their role in chronic renal rejection is poorly underst ood. Recently, distinct phenotypes of MCs have been described in humans by the demonstration of one protease, chymase. Hence, we questioned whether ch ymase in MCs could play a role in the pathogenesis of renal rejection in hu mans. :Methods. We investigated MC chymase expression and MC phenotypes, us ing immunohistochemical single- and double-staining techniques, in nephrect omy (N = 13) and biopsy (N = 8) specimens of human rejected kidneys. Tissue chymase levels were determined by enzymatic assay for chymase activity. We also examined the association between MC chymase expression and the degree of interstitial fibrosis in these renal allografts. Results. Based on chym ase positivity, rejected kidneys were divided into two groups, a chymase-ne gative [Chy(-)] group and a chymase-positive [Chy(+)] group. Quantitative a nalysis showed that the number of chymase-positive MCs and tissue chymase r evers were significantly higher in the Chy(+) group than in the Chy(-) grou p. Furthermore, the interstitial fibrotic area in the Chy(+) group was sign ificantly larger than that in the Chy(-) group. Immunodouble staining analy sis also demonstrated that a new MC phenotype: positive for chymase but neg ative for tryptase, was present in the human rejected kidney. Conclusions; These results show that increased expression of chymase in MCs is related t o the severity of interstitial fibrosis in human rejected kidneys.