Relationship Between the Pulmonary Neurotrophins Level and Airway Neural Plasticity in Respiratory Syncytial Virus Infected Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHAO Ranran ,  PANPinhua , QINQingwu , WANG Hui , HU Chengping.

The Respiratory Department of Xiangya Hospital, Centre South University. Changsha, Hu’nan,410008, China;

Corresponding author：

PANPinhua, Email: pinhuapan668@hotmail.com

Keywords：

Airway hyperresponsiveness; Airway neural plasticity; Asthma; Neurotrophin; Respiratory syncytial virus

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Objective To study the concentration of neurotrophins( including NGF, BDNF, NT3 and NT4) in the lung of SD rats infected by respiratory syncytial virus( RSV) , and to explore the relationship between the concentration of the neurotrophins, airway hyperresponsiveness and airway neural plasticity.Methods Twenty SD newborn rats were randomly divided into a control group and a RSV-infected group with ten rats in each group. The RSV-infected group were infected with 5 ×104 TCID50/0. 1 mL RSV each week. After 8 weeks, the bronchial responsiveness of the SD rats was assessed. The bronchial inflammation was assessed by HE staining with left lung. Synaptophysin and neurofilament expressions in the lung of SD rats were assayed by the immunohistochemistry staining. In situ hybridization was used to detect the RSV RNA in the lung. The concentration of neurotrophins in the lung of SD rats were detected by ELISA. Results The RSV-infected group showed elevated airway hyperresponsiveness and more inflammatory cells infiltrated in the lung; In situ hybridization showed positive signal of RSV RNA in lung interstitium of the RSV-infected rats. Synaptophysin and neurofilame levels in the airway were increased in the RSV-infected group. Supernatant levels of NGF and BDNF were significantly increased compared with the control group ( P lt;0. 05) . The NT3 and NT4 levels had no significant difference in all groups. The expressions of NGF and BDNF were positively related to the expressions of synaptophysin( r1 = 0. 892, r2 = 0. 995, P lt; 0. 05) and neurofilament( r1 = 0. 949, r2 =0. 936, P lt;0. 05) , also positively related to the airway hyperresponsiveness ( r1 =0. 929, r2 = 0. 910, P lt; 0. 05) . Conclusion RSV infection results in increased expressions of NGF and BDNF in the lung, which are correlated to the change of airway neural plasticity and airway hyperresponsiveness.

Citation： ZHAO Ranran,PANPinhua,QINQingwu,WANG Hui,HU Chengping.. Relationship Between the Pulmonary Neurotrophins Level and Airway Neural Plasticity in Respiratory Syncytial Virus Infected Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(2): 141-145. doi: Copy

1.	Ogra PL. Respiratory syncytial virus: The virus, the disease and the immune reponse. Paediatr Respir Rev, 2004, 5( suppl A) : S119-S126.
2.	Gern JE. Mechanisms of virus-induced asthma. J Pediatr, 2003, 142 ( suppl 2) : S9-S13.
3.	Johnston SL, Pattenmore PK, Sanderson G, et a1. The relationship between upper respiratory infections and hospital admissionss for asthma: a time-trend anylysis. Am J Respir Crit Care Med, 1996 ,154( 3 Pt 1) : 654-660.
4.	KerzelS,P　uth G, Nockher WA, et al. Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol, 2003, 28: 170-178.
5.	Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr, 1993, 23: 50-79.
6.	Shen XY, Pan PH, Wu ES, et al. Effects of respiratory syncytial virus infection on the airway neuronal plasticity and its relationship to the bronchial hyperresponsiveness in rats. Chin Med J( Engl) ,2006, 119: 156-159.
7.	Hu CB, Wedde-Beer K, Auais A, et al. Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. Am J Physiol Lung Cell Mol physiol, 2002, 283: L494-L502.
8.	Hamelmann E, Schwarze J, Takeda K, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med, 1997 ,156: 766-775.
9.	沈丹华, 廖晓耘, 刘艳丽, 等. 胎盘部位过度反应及胎盘部位结节的临床病理分析, 中华病理学杂志, 2004, 33: 441-444.
10.	Simoes EA. Respiratory syncytial virus infection. Lancet, 1999, 354 :847-852.
11.	Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med, 2005, 171: 137-141.
12.	Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci, 2001, 24: 677-736.
13.	Delcroix JD, Valletta J, Wu C, et al. Trafficking the NGF signal:implications for normal and degenerating neurons. Prog Brain Res,2004, 146: 3-23.
14.	Huang EJ, Wilkinson GA, Fari　as I, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC.Development, 1999, 126: 2191-2203.
15.	Ringstedt T, Ib　　ez CF, Nosrat CA. Role of brain-derived neurotrophic factor in target invasion in the gustatory system. J Neurosci, 1999, 19: 3507-3518.
16.	Piedimonle G. Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. Pediatr Infect Dis J, 2003, 22: S66-S75.
17.	Tortorolo L, Langer A, Polidori G, et al. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med, 2005, 172: 233-237.
18.	Hoffman PN. Distinct Roles of Neurofilament and Tubulin Gene Expression in Axonal Growth. Ciba Found Symp, 1988,138: 192-204.
19.	de Vries A, van Rijnsoever C, Engels F, et al. The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs. Br J Pharmacol, 2001 , 134 :771-776.
20.	de Vries A, Dessing MC, Engels F, et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperrespon-siveness in guinea pigs. Am J Respir Crit Care Med, 1999, 159: 1541-1544.
21.	Friberg SG, Olgart H　glund C, Gustafsson LE. Nerve growth factor increase airway responssives and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea pig model.Acta Physiol Scand, 2001, 173: 239-245.
22.	Ann NY. Neurotrophins in Allergic Airway Dysfunction What the Mouse Model Is Teching Us. Acad Sci, 2003, 992: 241-249.
23.	潘频华, 王慧, 胡成平. 呼吸道合胞病毒感染大鼠脊髓背根节突触囊泡素的表达与气道反应性的关系. 中国呼吸与危重监护杂志, 2007, 6: 294-297.
24.	Randolph CL, Bierl MA, Isaacson LG. Regulation of NGF and NT3 protein expression in peripheral targets by sympathetic input. Brain Res, 2007, 1144: 59-69.

1. Ogra PL. Respiratory syncytial virus: The virus, the disease and the immune reponse. Paediatr Respir Rev, 2004, 5( suppl A) : S119-S126.
2. Gern JE. Mechanisms of virus-induced asthma. J Pediatr, 2003, 142 ( suppl 2) : S9-S13.
3. Johnston SL, Pattenmore PK, Sanderson G, et a1. The relationship between upper respiratory infections and hospital admissionss for asthma: a time-trend anylysis. Am J Respir Crit Care Med, 1996 ,154( 3 Pt 1) : 654-660.
4. KerzelS,P　uth G, Nockher WA, et al. Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol, 2003, 28: 170-178.
5. Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr, 1993, 23: 50-79.
6. Shen XY, Pan PH, Wu ES, et al. Effects of respiratory syncytial virus infection on the airway neuronal plasticity and its relationship to the bronchial hyperresponsiveness in rats. Chin Med J( Engl) ,2006, 119: 156-159.
7. Hu CB, Wedde-Beer K, Auais A, et al. Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. Am J Physiol Lung Cell Mol physiol, 2002, 283: L494-L502.
8. Hamelmann E, Schwarze J, Takeda K, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med, 1997 ,156: 766-775.
9. 沈丹华, 廖晓耘, 刘艳丽, 等. 胎盘部位过度反应及胎盘部位结节的临床病理分析, 中华病理学杂志, 2004, 33: 441-444.
10. Simoes EA. Respiratory syncytial virus infection. Lancet, 1999, 354 :847-852.
11. Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med, 2005, 171: 137-141.
12. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci, 2001, 24: 677-736.
13. Delcroix JD, Valletta J, Wu C, et al. Trafficking the NGF signal:implications for normal and degenerating neurons. Prog Brain Res,2004, 146: 3-23.
14. Huang EJ, Wilkinson GA, Fari　as I, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC.Development, 1999, 126: 2191-2203.
15. Ringstedt T, Ib　　ez CF, Nosrat CA. Role of brain-derived neurotrophic factor in target invasion in the gustatory system. J Neurosci, 1999, 19: 3507-3518.
16. Piedimonle G. Contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection. Pediatr Infect Dis J, 2003, 22: S66-S75.
17. Tortorolo L, Langer A, Polidori G, et al. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med, 2005, 172: 233-237.
18. Hoffman PN. Distinct Roles of Neurofilament and Tubulin Gene Expression in Axonal Growth. Ciba Found Symp, 1988,138: 192-204.
19. de Vries A, van Rijnsoever C, Engels F, et al. The role of sensory nerve endings in nerve growth factor-induced airway hyperresponsiveness to histamine in guinea-pigs. Br J Pharmacol, 2001 , 134 :771-776.
20. de Vries A, Dessing MC, Engels F, et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperrespon-siveness in guinea pigs. Am J Respir Crit Care Med, 1999, 159: 1541-1544.
21. Friberg SG, Olgart H　glund C, Gustafsson LE. Nerve growth factor increase airway responssives and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea pig model.Acta Physiol Scand, 2001, 173: 239-245.
22. Ann NY. Neurotrophins in Allergic Airway Dysfunction What the Mouse Model Is Teching Us. Acad Sci, 2003, 992: 241-249.
23. 潘频华, 王慧, 胡成平. 呼吸道合胞病毒感染大鼠脊髓背根节突触囊泡素的表达与气道反应性的关系. 中国呼吸与危重监护杂志, 2007, 6: 294-297.
24. Randolph CL, Bierl MA, Isaacson LG. Regulation of NGF and NT3 protein expression in peripheral targets by sympathetic input. Brain Res, 2007, 1144: 59-69.

Chinese Journal of Respiratory and Critical Care Medicine

Relationship Between the Pulmonary Neurotrophins Level and Airway Neural Plasticity in Respiratory Syncytial Virus Infected Rats

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