Association between hemosiderin deposition and blood vessel regression during involution of foreign-body granuloma. Histochemical and ultrastructural study.

We have characterized the sequence of events resulting in vessel occlusion and stasis of blood flow during involution of a foreign-body granuloma using histochemistry and electron microscopy. In the microvascular bed of the granulation tissue accompanying the progressive resorption of an implanted collagen sponge, endothelial cells protruded into the vascular lumen, resulting in the occlusion of the lumens of venules and capillaries. Examination of sections stained by the TUNEL method showed brown-yellow stained structures in the vascular lumen during regression of blood vessels. However, the ultrastructural profiles of endothelial cells effectively involved in the vessel occlusion showed none of the cardinal morphological features of apoptosis. These endothelial cells which displayed remarkable indentations of their nuclei in the form of nuclear pinches and/or deep pockets bulged conspicuously into the lumen. Such endothelial cells served as effective valves by protruding into the lumens of small blood vessels, and eventually the vessels were completely plugged by red blood cells. However, protruding endothelial cells subsequently shed into the vascular lumen by deviating themselves from the constitution of the vessel wall. The endothelial cells undergoing apoptosis were removed by intraluminal macrophages. Between the 130 and 140 day, the occurrence of small vessels tightly packed with erythrocytes reached a peak value in the granulation tissue and was accompanied by hemosiderin deposits. The plugged vessels were frequently associated with erythrocyte extravasation, leading to openings between degenerated endothelial cells due to the disappearance of endothelial cytoplasmic projections. Extravasated erythrocytes were rapidly eliminated by phagocytic cells such as mononuclear macrophages and multinucleated giant cells, and ended as hemosiderin deposits in granulation and/or scar tissue at the end of the experimental period (130-140 days). The morphological analysis of this regression sequence suggests that the protrusion of endothelial cells with the nuclear deformation is a mechanism contributing to the occlusion of blood vessels and consequently leads to erythrocyte extravasation.