IMMUNOHISTOCHEMICAL STUDY OF RAT RENAL INTERSTITIAL FIBROSIS INDUCED BY REPEATED INJECTION OF CISPLATIN, WITH SPECIAL REFERENCE TO THE KINETICS OF MACROPHAGES AND MYOFIBROBLASTS

Progressive renal interstitial fibrosis occurs following tissue injury , resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg body weight, once weekly) was investigated immunohistochemically. During the 10-wk injection period, epithelial damage of the proximal renal tubules in the corticomedulla ry junction was seen, followed by cystic dilation of the affected tubu les. During the g-wk recovery period following the seventh injection, the size of the dilated lumina was diminished and atrophic tubules lin ed by regenerating epithelial cells appeared. Morphometrical analysis revealed that fibrosis began to develop around the dilated renal tubul es in the injection period and was more advanced in the following reco very period. Coinciding with development of fibrotic tissues, the numb er of ct-smooth muscle actin-positive myofibroblasts was significantly increased in the areas compared to that of controls. In the injection period, despite a significant increase in myofibroblast number, an el evation of ED-1 (primary antibody)-positive macrophage number was not observed. In the recovery period, however, a significant elevation of macrophage number was noticed in markedly advanced interstitial fibros is. This suggests that rapid expansion of the macrophage population, p robably resulting from release from myelosuppression due to CDDP, migh t contribute in part to development of myofibroblasts, leading to the augmented fibrosis in the recovery period.