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-μm-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.