Background. Mast cells (MCs) have been implicated in the pathogenesis of at
herosclerosis and tissue fibrosis. However. the role of MC in the developme
nt of renal fibrosis has not been fully elucidated. Stem cell factor (SCF;
the ligand for MC c-kit receptor) is thought to attract and activate MCs.
Methods. The intensity of MC infiltration and SCF expres sion in renal biop
sies from 56 patients with different forms of primary and secondary glomeru
lonephritis and five controls were investigated by immunohistochemistry, us
ing a monoclonal anti-human MC tryptase antibody and a polyclonal antihuman
SCF antibody.
Results. A large number of MCs were detected in the renal interstitium of t
he diseased kidneys, Immunostainable SCF was detected in tubular as well as
interstitial cells. MC infiltration was significantly higher in glomerulon
ephritis (16.9 +/- 10.2 cells/ field) compared with controls (2.8 +/- 2.1 c
ells/field, P = 0.03). Similarly. immunostainable SCF was 0.6 +/- 0.3% for
controls and 3.3 +/- 2.1% in the glomerulonephritis group (P = 0.02). MC in
filtration was highly correlated with SCF expression in diseased kidneys (r
= 0.93, P = 0.0001). Double immunostain showed them to colocalize in some
interstitia cells. Analysis of MC proliferation proliferating cell nuclear
antigen (PCNA) positivity] and apoptosis (in situ end labeling of DNA) show
ed these cells to be terminally differentiated. Both MCs and SCF were corre
lated with interstitial fibrosis (R = 0.71 for MC and R = 0.62 for SCF, P =
0.0001) and interstitial a-smooth muscle actin (R = 0.69 for MC and R = 0.
60 for SCF P = 0.0001). Using regression analysis, the number of MC infiltr
ation was found to be a very powerful determinant of interstitial fibrosis
in the glomerulonephritis group (R-2 = 91.4%).
Conclusion. MCs as an infiltrating hematopoietic cell and its growth factor
(SCF) seem to be up-regulated in glomerulonephritis, and may play a role i
n the development of renal fibrosis.