Proliferative responses of endothelial cell populations to experimentally induced inflammatory lesions of gingival connective tissues in the cynomolgus monkey (Macaca fascicularis)

Abstract

Endothelial cells exhibit heterogeneous and tissue-selective responses to injury and inflammation. The regulation of the size of endothelial populations in specific tissue sites is poorly characterized, particularly in soft connective tissues adjacent to bone. To investigate the effect of a primarily lymphocytic infiltrate on endothelial cell proliferation and growth of blood vessels, a primate model was used that reliably exhibits localized, distinct inflammatory, and destructive lesions in isolated sites of mucosal connective tissues adjacent to bone and epithelium around teeth. Three Cynomolgus monkeys with healthy periodontium and two with spontaneously occurring inflammation or induced connective tissue destruction were pulse labeled with 3H-thymidine. Morphometric analyses of radioautographs from mid-sagittal supra-alveolar gingival connective tissues of incisor teeth were performed in sites subjacent to junctional, sulcular, and oral epithelium, in the body of the lamina propria and just superior to the alveolar bone crest. Subjacent to the sulcular epithelium there was a statistically significant (P < 0.01) increase in lymphocyte density between health and inflammation. The percentage of endothelial cells incorporating 3H-thymidine label (LI) and the number of blood vessels per unit area were significantly increased in this same site in inflamed samples (P < 0.02) but were not elevated further in lesions in which there was destruction of soft connective tissues. However, there was no increase of the numbers or the cross-sectional areas of blood vessels between samples of inflamed and destroyed tissues. 1) Experimentally induced inflammation and connective tissue destruction in the gingival connective tissues of Cynomolgus monkeys is associated with site-specific perturbations in the turnover of endothelial cells that is closely linked to lymphocytic infiltration; 2) the vascular response is a generalized increase in endothelial cell proliferation and blood vessel numbers but not lumen size or number of endothelial cells, suggesting the existence of homeostatic controls for preservation of the whole population in a steady state.