Co-production of vascular endothelial cadherin and inducible nitric oxide synthase by endothelial cells in periapical granuloma.
AIM: To clarify the mechanisms of inflammatory cell migration in human periapical granulomas by examining vascular endothelial (VE) cadherin and inducible nitric oxide synthase (iNOS)-producing cells. METHODOLOGY: Periapical tissues were obtained from patients during endodontic surgery and were divided into two portions. After fixing the tissues with acetone or 4% paraformaldehyde in phosphate-buffered saline, 5-microm-thick paraffin or cryostat sections were prepared, respectively. The paraffin sections of the inflamed tissues were evaluated histologically with haematoxylin-eosin stains. Cryostat sections of the tissue, diagnosed as periapical granulomas, were then examined by either immunohistochemistry using anti-human VE-cadherin or iNOS antibodies (Abs) for the characterization of infiltrating cells. In addition, co-localization of VE-cadherin and iNOS production was also analysed by two-colour immunofluorescence image analysis. RESULTS: Endothelial cells were strongly stained with iNOS Abs. Macrophages, lymphocytes, polymorphonuclear leucocytes and fibroblasts also exhibited iNOS production. These iNOS-positive cells accumulated around the blood vessels. On the other hand, VE-cadherin production was exhibited in only endothelial cells. Two-colour immunofluorescence image analysis using VE-cadherin and iNOS Abs demonstrated that iNOS-producing endothelial cells also showed VE-cadherin production. CONCLUSIONS: Vascular endothelial-cadherin produced by endothelial cells could be regulated by iNOS-producing cells in periapical granulomas and might play a pivotal role in vascular permeability.