Endothelial proliferation in inflammation. I. Autoradiographic studies following thermal injury to the skin of normal rats.

Endothelial prolifertion was studied in sites of acute inflammation induced by necrotizing (60 C for 20 seconds) or mild (54 C for 20 seconds) thermal injury to the skin of rsts. DNA synthesis in endothelial cells was assayed 6 hours to 10 days following injury by quantitation of the (3)H-thymidine labeling indices on 2-mu Epon section autoradiographs. In lesions induced at 60 C for 20 seconds, increase in DNA synthesis in small vessels around the necrotic tissue began at 1 day and became significant at 2 and 3 days (10 to 12% for endothelial cells, 9% for perivascular cells). This increased endothelial replication resulted in the formation of new blood vessels by 5 to 7 days. Endothelial labeling diminished progressively after 3 days, as the epidermis regenerated. Foci completely covered by new epidermis consistently showed lower labeling indices than those which were not reepithelialized. Mild thermal injury (54 C for 20 seconds) also resulted in significant increases in endothelial labeling (6%), but the labeling was present mainly in superficial vessels and was not followed by neovascularization. The findings with mild injury are consistent with data that vascular leakage from superficial vessels is due to direct, albeit delayed, endothelial damage. Electron microscopic studies confirmed labeling in endothelial cells and indicated that ultrastructural alterations that were previously ascribed to activation, recovery, or regenerative transformation of endothelium represent, in the main, endothelial proliferation.