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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Wu
XinQun
X
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Myers
Allen C
AC
Goldstone
Andrew C
AC
Togias
Alkis
A
Sanico
Alvin M
AM
D017252:CD3 Complex; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D009297:Nasal Mucosa / Q000294:innervation / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism*; D012697:Serine Endopeptidases; D053802:Tryptases
D017252:CD3 Complex; D047091:Eosinophil Granule Proteins; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D012697:Serine Endopeptidases; D053802:Tryptases