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Comparative Study
, 62 (4), 489-94

Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

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Comparative Study

Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

Aviv D Goldbart et al. Pediatr Res.

Abstract

Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p<0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p<0.01), and substance P concentrations in OSA patients were higher than in RI (p<0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.

Figures

Figure 1
Figure 1
Expression of mRNA for neurotrophic factors NGF, BDNF, NT3, and for TrkA in adenotonsillar tissues harvested from patients with either RI or OSA, and shown as ratios with GAPDH as housekeeping gene. Significantly higher NGF (■, *p < 0.001) and trkA (□; *p = 0.001) expression occurred in OSA patients (n = 32) compared with RI patients (n = 25), with similar expression of BDNF formula image and NT3 formula image
Figure 2
Figure 2
(A) Mean NK1 receptor mRNA expression in adenotonsillar tissues obtained from children with obstructive sleep apnea (OSA; n = 32) and recurrent infections shown as ratios with GAPDH as housekeeping gene (RI; n = 25; OSA vs. RI: *p < 0.002). (B) Mean NK1 receptor protein expression in adenotonsillar tissues obtained from children with OSA (n = 20) and recurrent infections (RI; n = 20) (*p < 0.001).
Figure 3
Figure 3
Illustrative examples of immunoreactivity patterns of the NK1 receptor in tonsils obtained from patients with either RI (A) or OSA (B); n = 5/group. Enhanced immunoreactivity of NK1 receptor is apparent in OSA, and is mainly observed within tonsillar germinal centers (C). No staining was observed within germinal centers of patients with RI. Scale bar shown on left upper corner of each image. Scale bar = 100 μm, all panels.
Figure 4
Figure 4
Mean substance P concentrations in adenotonsillar tissues obtained from children with obstructive sleep apnea (OSA; n = 32) or recurrent tonsillitis (n = 23). (*p < 0.003).
Figure 5
Figure 5
Schematic illustration of putative neurotrophic factor-neurokinin pathways and their effects on the developing human upper airway lymphoid tissues. Early life exposures to viruses may lead in a genetically predisposed population to exaggerated tissue specific inflammation/proliferation following subsequent environmental/viral exposures.

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