IMMUNOHISTOCHEMICAL OBSERVATIONS ON THE KINETICS OF MACROPHAGES AND MYOFIBROBLASTS IN RAT RENAL INTERSTITIAL FIBROSIS INDUCED BY CIS-DIAMMINEDICHLOROPLATINUM

It has been speculated elsewhere that growth factors produced by macro phages in response to tissue damage induce a modulation of pre-existin g fibroblasts into myofibroblasts, leading to fibrosis. The developmen t of these cells in cis-diamminedichloroplatinum (CDDP)-induced rat re nal interstitial fibrosis was observed immunohistochemically. In the c ortico-medullary junction, nuclear changes and epithelial necrosis of the proximal renal tubule (mainly the P-3 segment) were seen on days 1 and 4 after a single dose (6 mg/kg body weight) of CDDP, and regenera ting epithelium appeared on day 7. Gradually developing fibrosis was o bserved around the affected tubules on days 14 and 28. The increase in fibrosis was confirmed by histometrical analysis. The number of ED-1 (primary antibody) positive macrophages reached a peak in the affected cortico-medullary junction on day 7 and this was accompanied by an in crease in muscle actin-positive myofibroblasts. On days 14 and 28, mac rophages had declined in number, but the number of muscle actin-positi ve myofibroblasts in the fibrotic area was still high as compared with control values. Cytoplasmic myofilaments were observed in myofibrobla sts by electron microscopy. These findings suggest that the myofibrobl asts participate in renal interstitial fibrosis in the rat, and that t heir appearance may be related to macrophage infiltration in response to tubular injury, at least in the early stages of fibrosis.