Distribution of nerve growth factor, pro-nerve growth factor, and their receptors in human salivary glands

Nerve growth factor (NGF) is a pluripotent mediator that is present in a range of human tissues. Nerve growth factor was originally considered important only in neuronal homeostasis and pathophysiology, but later it was also implicated in the pathophysiology of inflammation, epithelial differentiation, and wound healing. In this study, the distribution of nerve growth factor beta (NGF-beta) and pro-NGF, and their receptors tyrosine kinase A (TrkA) and p75NTR was examined in human parotid, submandibular, sublingual, and labial salivary glands by immunohistochemistry. Intercalated, striated, and collecting-ducts in all gland types showed strong staining for pro-NGF but only weak cytoplasmic or sparse nuclear staining for NGF-beta. Tyrosine kinase A was strongly expressed in the ducts of all gland types, whereas p75NTR expression was mainly confined to collecting ducts. In acini, no or only weak cytoplasmic staining was found for all markers, and some nuclei stained positive for NGF-beta, pro-NGF, and TrkA. Western blotting of saliva showed secretion of several forms of pro-NGF, while no mature NGF-beta was detected. Salivary pro-NGF may play a role in oral wound healing.