Roles Of Bronchopulmonary C-fibers In Airway Hyperresponsiveness And Airway Remodeling

PART Ⅰ ROLES OF BRONCHOPULMONARY C-FIBERS IN LUNG VENTILATION FUNCTION AND AIRWAY HYPERRESPONSIVENESSBackground: Asthma is characterized by chronic airway inflammation,airway hyperresponsiveness(AHR),and airway remodeling.While exposure of house dust mites(HDM)is a common cause of asthma,the pathogenesis of the HDM-induced asthma is not fully understood.Bronchopulmonary Cfibers(PCFs)contribute to the neurogenic inflammation,viral infection induced-persistent AHR,and ovalbumin induced collagen deposition largely via releasing neuropeptides,such as substance P(SP).However,PCF roles in the pathogenesis of the HDM-induced asthma remain unexplored.The goal of this study was to determine what role PCFs played in generating these characteristics.Methods: BALB/c mice were grouped according to PCF-intact and-degenerated mice with and without chronic HDM exposure.We compared the following variables among four groups: 1)basic lung ventilation function;2)lung ventilation function in hypoxia and hypercapnia condition;3)AHR and pulmonary SP.Results: We found that HDM evoked AHR associated with upregulation of pulmonary SP,downregulaton of lung ventilation function in hypercapnia condition.PCF degeneration decreased the HDM-induced changes in AHR,pulmonary SP,but failed to significantly affect the lung ventilation function in hypercapnia condition.HDM and KPCF did not significantly affect the basic lung ventilation function.Conclusion: PCFs participate in the mechanism of AHR induced by HDM,may via releasing neuropeptides,such as SP.PART Ⅱ ROLES OF BRONCHOPULMONARY CFIBERS IN AIRWAY REMODELING AND AIRWAY INFLAMMATION INDUCED BY HOUSE DUST MITE Background: Asthma is characterized by chronic airway inflammation,airway hyperresponsiveness(AHR),and airway remodeling.In our previous study,we found PCFs participated in the mechanism of AHR induced by HDM,may via releasing neuropeptides,such as SP.The goal of present study was to determine what role PCFs played in airway remodeling and airway inflammation.Methods: BALB/c mice were grouped as first part: CtrlIntact,HDMIntact,CtrlPCFX,HDMPCFX..We compared the following variables among the PCFintact and-degenerated BALB/c mice with and without chronic HDM exposure: 1)airway smooth muscle(ASM)mass;2)tracheal contraction evoked by high potassium and methacholine in vitro;3)pulmonary inflammatory cells;and 4)epithelium thickening(Clara cells and ciliated cells)and mucus secretion.Results: We found that HDM evoked airway inflammation associated with upregulation of ASM mass increase,Clara cells layer thickenings,and mucus hypersecretion,but failed to affect the ciliated cells.PCF degeneration decreased the HDM-induced changes in inflammation,and ASM mass,but failed to significantly affect the epithelium thickening and mucus hypersecretion.HDM and KPCF did not significantly affect the tracheal contraction evoked by high potassium and methacholine in vitro.Conclusion: Our data suggest an involvement of PCFs in the mechanisms by which HDM induces allergic asthma via airway inflammation,AHR,and airway remodeling.Our finding confirms a neuroimmune interaction in asthmatic development and highlights a new potential way to therapeutically intervene ASM remodeling by inhibition of PCFs.