Localization of nerve growth factor and its receptors in the human nasal mucosa

Background: Nerve growth factor (NGF) is a pluripotent mediator, the levels of which are elevated in nasal lavage fluids of individuals with allergic rhinitis at baseline. Levels of NGF increase after allergen challenge. Objective: In the current study, we tested the hypotheses that mast cells are the main source of human nasal NGF, and that NGF can potentially affect mucosal elements other than nerves. Methods: Immunostaining with antibodies against NGF, tryptase, CD3, eosinophil cationic protein, and the high-affinity (tyrosine kinase A) and low-affinity (p75) receptors for NGF was performed by using human nasal turbinate sections. Results: Double immunofluorescence staining demonstrated NGF in only 2% (median) (1.3, 2.3; 25th, 75th percentiles) of mast cells, 0.2% (0, 0.4) of T cells, but in 62.2% (56.5, 68) of activated eosinophils. With immunohistology, NGF expression was consistently strongest in the submucosal glands and lesser in the epithelial lining. Both high-affinity and low-affinity receptors for NGF were localized not only on nerves, as expected, but also on nasal epithelium, submucosal glands, and some interstitial cells, but not on vascular endothelium. Conclusion: This study demonstrates that submucosal glands, nasal epithelium, and eosinophils constitute the major sources of NGF in the human nasal mucosa. That NGF receptors are found in cells other than nerves supports the notion that the role of this neurotrophin is broader than simple modulation of the sensorineural system. Clinical implications: The distribution of NGF and its receptors and its established release during allergic reactions suggest that this factor participates in the pathophysiology of allergic rhinitis.