Neural Expression and Increased Lavage Fluid Levels of Secretoneurin in Seasonal Allergic Rhinitis

Abstract

Secretoneurin is a neuropeptide potentially involved in migration of eosinophils, monocytes, and dendritic cells. Whether secretoneurin is present in the human airway mucosa and whether it is released at ongoing allergic airway inflammation is currently unknown. In patients with allergic rhinitis, we have explored the occurrence of secretoneurin in nasal mucosal biopsies and lavage fluids before and during natural allergen exposure. Immunohistochemical analysis revealed an abundance of nerves displaying secretoneurin immunoreactivity, which were distributed predominantly around blood vessels and submucosal glands. A majority of nerve fibers containing vesicular acetylcholine transporter, tyrosine hydroxylase, calcitonin gene-related peptide, and vasoactive intestinal peptide were also secretoneurin-immunoreactive, indicating a localization of secretoneurin in cholinergic, adrenergic, and sensory nerves. Lavage fluid levels of secretoneurin were increased at allergen exposure (p < 0.01-0.05). Levels of secretoneurin did not correlate with eosinophil cationic protein (rho = 0.1, p = 0.7). We conclude that secretoneurin has a widespread occurrence in nasal mucosal nerves of patients with seasonal allergic rhinitis and that increased nasal lavage fluid levels of secretoneurin may characterize ongoing allergen exposure. These data favor a role of secretoneurin in the local traffic of immune cells in human airway mucosa.

Distribution of neuropeptides in nasal and nasopharyngeal mucosa in patients with the post nasal drip syndrome

“…Serotonin as well as histamine, leukotrienes, prostaglandins and tryptase are released and account for the immediate airway allergy symptoms and it is often found in the case of hyperreflectoric rhinitis as well (9). That fact can suggest that serotonin as well as the substance P, has no significant influence on the post nasal drip pathogenesis, and it makes a significant difference from the described study results until now in the case of allergic and hyperreflectory rhinitis (7,8,9,10,16). …”

“…In the studies described in literature, CGRP is usually found in allergic and hyperreflectoric rhinitis (16,20). Calcitonin gene-related peptide is one of the neuropeptides that is released in the human nasal mucosa after trigeminal nerve stimulation.…”

“…C and Aδ fiber stimulation causes the release of neuropeptides. The release of neuropeptides by sensory nerve endings produces vasodilatation and increased vascular permeability, the phenomena primarily described in the rodents that have been collectively termed neurogenic inflammation (4,16,22).…”

Secretoneurin Induces Airway Mucus Hypersecretion by Enhancing the Binding of EGF to NRP1

“…Secretoneurin-immunoreactive nerve fibers in the respiratory tract have been found to co-localize with vesicular acetylcholine transporters, tyrosine hydroxylase, calcitonin gene-related peptide, and vasoactive intestinal peptide, indicating that secretoneurin is localized to cholinergic, adrenergic, and sensory nerves. Immunohistochemical studies of mucosal biopsies and nasal lavage fluid have indicated a predominant distribution of SN around submucosal glands in the airways of patients with seasonal allergic rhinitis [9]. Allergen exposure or bronchial histamine challenge increases the sputum levels of secretoneurin [18].…”

“…According to immunohistochemical analyses, a large number of SN-positive neurocytes are present in allergic rhinitis. In addition, based on evidence that SN produces a significant increase in nasal lavage fluid in seasonal allergic rhinitis patients after contact with allergens [9], SN has been considered a reliable marker of allergenic stimulation. However, the relationship between SN and the secretion of airway mucin remains unclear.…”