Neurotrophins and tonsillar hypertrophy in children with obstructive sleep apnea.
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.
Goldbart
Aviv D
AD
Department of Pediatrics, Kosair Children's Hospital Research Institute, and Department of Surgery, Division of Ear Nose and Throat, University of Louisville, Louisville, Kentucky 40202, USA.
Mager
Edward
E
Veling
Maria C
MC
Goldman
Julie L
JL
Kheirandish-Gozal
Leila
L
Serpero
Laura D
LD
Piedimonte
Giovanni
G
Gozal
David
D
D000234:Adenoids / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006984:Hypertrophy; D008297:Male; D020932:Nerve Growth Factor / Q000032:analysis; D009414:Nerve Growth Factors / Q000032:analysis* / Q000235:genetics; D014066:Palatine Tonsil / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D020917:Receptor, trkA / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D013373:Substance P / Q000032:analysis; D014069:Tonsillitis / Q000378:metabolism / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D013373:Substance P; D020932:Nerve Growth Factor; D020917:Receptor, trkA