To clarify the relation between macrophage and myofibroblast involvement in various myocardial diseases, the authors investigated the kinetics of these cells in the healing (scar tissue formation) following isoproterenol-induced myocardial injury in rats. Alpha-smooth muscle actin (alpha-SMA) expressing myofibroblasts were seen at the border of the affected area and appeared in the greatest numbers on days 3-7 post-injection, followed by a gradual decrease by day 35. The peak on day 3 was consistent with the timing of the highest proliferative activity of myofibroblasts. The number of ED1-positive macrophages began to increase as early as day 1, reaching a peak on day 3 within the injured myocardium. The expansion of ED1-positive macrophages preceded an increased number of alpha-SMA-positive myofibroblasts suggesting that myofibroblast proliferation and activation may be mediated by factors released by ED1-positive macrophages in response to myocardial injury. The number of ED2-positive tissue-fixed, resident macrophages gradually, increased from day 3 post-injection, and peaked on day 14, but the number of ED2-positive macrophages was consistently fewer than that of ED1-positive macrophages during the 35 day-observation period after the injection. The labelling index of the ED2-positive cells was maximal on day 14, indicative of local proliferation of resident macrophages. In the healing process after myocardial injury, ED1-positive macrophages increase markedly in the early stages: ED2-positive macrophages appear later.
A four-year-old, spayed female Yorkshire terrier was presented with a two-month history of lameness in the left forelimb, circling and falling. A magnetic resonance imaging (MRI) examination 11 days after presentation revealed dilation of the right lateral ventricle. Following euthanasia, which was performed about 10 months after the onset of clinical signs, there was gross evidence of degeneration and cavitation of the cerebrum and dilation of the lateral ventricle on the right side. Microscopically, cavitation and necrosis were observed in the white and grey matter of the right cerebrum and there was abundant gemistocytic and fibrillary astrocytosis. Haemorrhage and marked perivascular cuffing with mononuclear cells were found in the mesencephalon. Inflammatory lesions consisting of lymphocytic infiltration and glial proliferation were also present in the dorsal funiculus of the cervical spinal cord. This case was diagnosed as necrotising encephalitis in the Yorkshire terrier (NEYT) with involvement of the spinal cord. NEYT is a chronic progressive neurological disorder, resulting from widespread, destructive non-suppurative inflammation of the central nervous system of unknown cause. In the past decade, 12 cases have been documented in adult to aged Yorkshire terriers. Computed tomography and MRI can detect the characteristic multifocal cavitations and ventriculomegaly, facilitating premortem diagnosis.
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 corticomedullary junction was seen, followed by cystic dilation of the affected tubules. During the 8-wk recovery period following the seventh injection, the size of the dilated lumina was diminished and atrophic tubules lined by regenerating epithelial cells appeared. Morphometrical analysis revealed that fibrosis began to develop around the dilated renal tubules in the injection period and was more advanced in the following recovery period. Coinciding with development of fibrotic tissues, the number of alpha-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 elevation 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 fibrosis. This suggests that rapid expansion of the macrophage population, probably resulting from release from myelosuppression due to CDDP, might contribute in part to development of myofibroblasts, leading to the augmented fibrosis in the recovery period.
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