Lymphoedema of the rabbit ear following partial and complete lymphatic blockade: its effects on fibrotic development, enzyme types and their activity levels

The dorsal surface of the rabbit ear was found to be a suitable place for the production of long-lasting lymphoedema. Its major tissues (skin and subcutaneous) are those to which secondary lymphoedema is confined in clinical situations. After 32 weeks of partial lymphatic blockade total tissue activity levels of neutral proteinase and β-glucuronidase were depressed while alkaline phosphatase was elevated. Subsequent complete lymphatic blockade for a further 5 weeks resulted in severe fibrosis of the s.c. tissues. The total tissue activity levels of 3 characteristic lysosomal macrophage hydrolases - acid protease, β-glucuronidase and acid phosphatase - were significantly increased. There were strong correlations between the activity levels of these enzymes and the extent of fibrosis, increased fibrosis being characterized by higher activity levels. This, together with other evidence, suggested - as fibrosis became more severe - the total number of macrophages increased, but a high proportion of these were nonstimulated. Since these cells (when stimulated) are normally responsible for the lysis of collagen and removal of fibrotic tissue, the impairment of their function as occurs in chronic lymphoedema results in further fibrosis and the continuation of the vicious circle.