Exaggerated Neurogenic Inflammation and Substance P Receptor  Upregulation in RSV-Infected Weanling Rats

King, Katherine A.; Hu, Chengping; Rodríguez, Maria M.; Romaguera, Rita L.; Jiang, Xiaobo; Piedimonte, Giovanni

doi:10.1165/ajrcmb.24.2.4264

Cited by 87 publications

(87 citation statements)

References 19 publications

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“…by depositing in each nostril 20 L of virus suspension that contained 3.5 ϫ 10 7 pfu/mL (12). For the studies with adenovirus, we inoculated the same volume and same titer of human adenovirus type 4 obtained from American Type Culture Collection (Manassas, VA) (22).…”

Section: Animalsmentioning

confidence: 99%

“…In particular, the local irritation of C-type nociceptive afferents in infected airways evokes bronchospasm, neurogenic inflammatory edema, and recruitment and activation of leukocytes (10). We showed previously that RSV infection amplifies the inflammatory and immunomodulatory effects of sensory nerves via both presynaptic (increased synthesis and release of substance P) and postsynaptic [up-regulation of neurokinin 1 (NK 1 ) receptors] mechanisms (11)(12)(13), both involving the overexpression of nerve growth factor by the infected respiratory epithelium (14).…”

mentioning

confidence: 99%

“…We reported previously that RSV infection in rats produces a strong potentiation of neurogenic-mediated inflammation by amplifying the synthesis and release of substance P (13) and the expression of NK 1 receptors on target cells (11,12), thus making the airways abnormally susceptible to the proinflammatory effects of this peptide primarily released from sensory nerves (11). This complex remodeling of sensorineural pathways in the respiratory tract is coordinated via increased expression of the prototypical neurotrophin nerve growth factor from infected epithelia (14).…”

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confidence: 99%

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Effect of Respiratory Syncytial Virus on Apnea in Weanling Rats

et al. 2005

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Apnea is a common complication of respiratory syncytial virus (RSV) infection in young infants. The purpose of this study was to determine whether this infection affects apnea triggered by sensorineural stimulation in weanling rats. We also studied which neurotransmitters are involved in this response and whether passive prophylaxis with a specific neutralizing antibody (palivizumab) confers protection against it. Weanling rats were inoculated intranasally with RSV, adenovirus, or virus-free medium. Changes in respiratory rate and apnea in response to nerve stimulation with increasing doses of capsaicin were measured by plethysmography. Capsaicin-induced apnea was significantly longer in RSV-infected rats at postinoculation days 2 (upper airways infection) and 5 (lower airways infection), and apnearelated mortality occurred only in the RSV-infected group. Reduction in the duration of apnea was observed after selective inhibition of central ␥-aminobutyric acid (GABA) type A receptors and neurokinin type 1 receptors for substance P. Prophylactic palivizumab protected against apnea and apnea-related mortality. These results suggest that sensorineural stimulation during RSV infection is associated with the development of apnea and apnea-related death in early life, whose mechanism involves the release of GABA acting on central GABA type A receptors and substance P acting on neurokinin type 1 receptors. Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infections in infants and young children and presents a large public health problem worldwide (1). Although most infections have a mild course, RSV can cause severe respiratory compromise, especially in patients with underlying cardiorespiratory conditions, and predisposes to the development of childhood asthma (2). Apnea can be the presenting sign of this infection, and its incidence varies between 16 and 25% of infected infants, with a particularly high risk associated with young age (Ͻ3 mo) and prematurity (3-5). Because of its ability to interfere with ventilatory control, it has been suggested that RSV infection may also be a precipitating factor in cases of sudden infant death (SID) (6-8), yet the pathophysiology of apnea associated with RSV infection remains unclear, and no specific prophylaxis or treatment is currently available to protect infants from this complication.Among the factors that influence airway function are neural control mechanisms, which can undergo dysregulation during and after viral respiratory infections (9). In particular, the local irritation of C-type nociceptive afferents in infected airways evokes bronchospasm, neurogenic inflammatory edema, and recruitment and activation of leukocytes (10). We showed previously that RSV infection amplifies the inflammatory and immunomodulatory effects of sensory nerves via both presynaptic (increased synthesis and release of substance P) and postsynaptic [up-regulation of neurokinin 1 (NK 1 ) receptors] mechanisms (11-13), both involving the overexpression of ner...

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Section: Animalsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Effect of Respiratory Syncytial Virus on Apnea in Weanling Rats

et al. 2005

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“…It has now been recognized by several epidemiologic studies that factors such as environmental smoking, allergies, and intercurrent respiratory infections are all associated with either transient or persistent hypertrophy of lymphadenoid tissue in the upper airways of snoring children (10 -12). Interestingly, all of these risk factors involve the generation of an inflammatory response, suggesting that the latter may promote the onset and maintenance of proliferative signals to lymphadenoid tissues.Bronchial-associated lymphoid tissue in the lungs of RSVinfected rats express high levels of the neurokinin 1 (NK1) receptor for substance P that is released from subepithelial sensory nerve fibers, a part of the nonadrenergic noncholinergic system (13,14). Furthermore, nerve growth factor (NGF), a major controller of sensorineural development and immuno-inflammatory responses, and its tyrosine kinase A receptor (trkA) are both overexpressed in rat lungs after respiratory syncytial virus (RSV) inoculation (15).…”

mentioning

confidence: 99%

“…Bronchial-associated lymphoid tissue in the lungs of RSVinfected rats express high levels of the neurokinin 1 (NK1) receptor for substance P that is released from subepithelial sensory nerve fibers, a part of the nonadrenergic noncholinergic system (13,14). Furthermore, nerve growth factor (NGF), a major controller of sensorineural development and immuno-inflammatory responses, and its tyrosine kinase A receptor (trkA) are both overexpressed in rat lungs after respiratory syncytial virus (RSV) inoculation (15).…”

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Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

et al. 2007

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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 Ͻ 0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p Ͻ 0.01), and substance P concentrations in OSA patients were higher than in RI (p Ͻ 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. O bstructive sleep apnea syndrome (OSA) is a common and highly prevalent disorder in the pediatric age range, affecting 2-3% of all children (1). Adenotonsillar hypertrophy is by far the major pathophysiological contributor to OSA in children (2,3), and adenotonsillectomy (T&A) currently remains the first line of treatment for children with OSA (4). If left untreated, OSA can result in serious morbid consequences that affect neurocognitive, behavioral and cardiovascular systems (5-9). However, the mechanisms underlying the regulation of benign follicular lymphoid proliferation and hyperplasia are so far extremely poorly understood, such that prediction of which children will develop adenotonsillar hypertrophy is impossible at this stage. It has now been recognized by several epidemiologic studies that factors such as environmental smoking, allergies, and intercurrent respiratory infections are all associated with either transient or persistent hypertrophy of lymphadenoid tissue in the upper airways of snoring children (10 -12). Interestingly, all of these risk factors involve the generation of an inflammatory response, suggesting that the latter may promote the onset and maintenance of proliferative signals to lymphadenoid tissues.Bronchial-associated lymphoid tissue in the lungs of RSVinfected rats express high levels of the neurokinin 1 (NK1) receptor for substance P that is released from subepithelial sensory nerve fibers, a part of the nonadrenergic noncholinergic system (13,14). Furthermore, nerve growth factor (NGF), a major controller of sensorineural development and immuno-inflammatory responses, and its tyrosine kinase A receptor (trkA) are both overexpressed...

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Association of Serum Albumin With Apnea in Infants With Bronchiolitis

et al. 2019

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Key Points Question Is serum albumin level associated with the risk of apnea in infants with bronchiolitis? Findings In this secondary analysis of a cohort of 1016 infants hospitalized for bronchiolitis, low serum albumin was statistically significantly associated with a higher risk of apnea during the hospitalization. This association was independent of known apnea risk factors (younger age, premature birth, and weight-for-age z score). Meaning Albumin levels may have a role in identifying apnea in bronchiolitis.

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Exaggerated Neurogenic Inflammation and Substance P Receptor Upregulation in RSV-Infected Weanling Rats

Cited by 87 publications

References 19 publications

Effect of Respiratory Syncytial Virus on Apnea in Weanling Rats

Effect of Respiratory Syncytial Virus on Apnea in Weanling Rats

Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

Association of Serum Albumin With Apnea in Infants With Bronchiolitis

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