The ineffectiveness of coumarin treatment on thermal oedema of macrophage-free rats.

The administration of silica prevents coumarin-stimulated lysis of accumulated abnormal protein. This impairs the resolution of thermal oedema which is normally increased with coumarin administration. Evidence suggests that there is a rapid differentiation and infiltration of monocytes into the tissues and that these are selectively retained. This is aided by coumarin which increases tissue permeability. Coumarin also injures the vascular endothelium of some vessels, allowing extra protein and fluid into the tissues. Death of recently differentiated macrophages and subsequent release of their lysosomal contents into the extra-cellular spaces may be responsible for the changes in serum enzyme levels. It would seem that macrophages are the only cells in which coumarin stimulates increased phagocytosis, enzyme production and proteolysis.