Roles of neurogenic and leukotriene-dependent inflammation in upper and lower airway allergic diseases
Objective To explore the roles of neurogenic and leukotriene-dependent inflammation in upper and lower airway allergic diseases.Methods Thirty nine female BALB/c mice were randomly divided into the upper airway allergic disease(SU)group(n=12),lower airway allergic disease(SL)group(n=12),combined upper and lower airway allergic disease(CUL)group(n=12)and control group(n=3).The upper,lower and combined upper and lower airway allergic disease models were induced by intraperitoneal injection of ovalbumin(OVA),the nasal and tracheal administration of OVA,and both intraperitoneal and nasal trachea administration of OVA,respectively.Each of the three allergic mice groups were further divided into model group,NI group,LI group and NLI group with 3 mice in each,and the last 3 groups were treated with substance p receptor antagonist(NI),leukotriene receptor antagonist(LI)and NI plus LI,respectively.On the d33 animals were sacrificed,the nasal lavage fluid(NLF)and bronchoalveolar lavage fluid(BALF)samples and the nasal mucosa and lung tissue samples were taken.Eosinophilic infiltration in nasal mucosa and lung tissue was observed by HE staining;the expression of CysLTR1 and NPR in the nasal mucosa and lungs was detected with immunohistochemistry;the levels of Cysteine leukotrienes,neurotrophic factors and neurotransmitters in NLF and BALF were measured by ELISA.Results Compared with the control group,the SU-model group and CUL-model group showed increased infiltration of eosinophils in the nasal mucosa and lungs,while eosinophils infiltration was observed in lung tissue of SL-model group.The expressions of NPR and CysLTR1 in nasal mucosa and lung tissue of the 3 model groups were higher than those of the control group.The levels of CysLTs,BDNF,NGF,CGRP,NKA,NKB and NP in NLF of SU-model and CU-model groups were higher than those in control group;while the levels in SU-NI,SU-LI and SU-NLI groups were lower than those in SU-model group.The levels of CGRP and NP in SU-NLI group were lower than those in SU-NI group and SU-LI group,the levels of NP in SL-model group were higher than those in control group,and the levels of NP in SL-NI,SL-LI and SL-NLI groups were lower than those in SL-model group.The levels of BDNF and NGF in CUL-NI,CUL-LI and CUL-NLI groups were lower than those in CUL-model group,the levels of CGRP and NKA in CUL-LI group and CUL-NLI group were lower than those in CUL-model group,and the levels of NKA in CUL-NLI group were lower than those in CUL-LI group.The NKB of CUL-NI,CUL-LI and CUL-NLI groups was lower than that of CUL-model group(all P<0.05).The NLF levels of CysLTs in SL-model and CUL-model groups were higher than those in control group;the levels of NGF,CGRP,NKA and NP in SL-model group were higher than that in control group;the level of CGRP in CUL-model group was higher than that in control group.The levels of CysLTs,NGF,CGRP,NKA and NP in SL-NI,SL-LI and SL-NLI groups were lower than those in SL-model group,and the levels of CysLTs in SL-NLI group were lower than those in SL-NI and SL-LI groups.The levels of CGRP in CUL-NI,CUL-LI and CUL-NLI groups were lower than those in CUL-model group(all P<0.05).Conclusion Upper airway inflammation can cause lower airway inflammation through neurogenic inflammation and leukotriene-dependent inflammation in allergic diseases,while lower airway inflammation hardly affects the upper airway.The intervention with neuropeptide receptors or leukotriene receptors antagonists may be able to treat airway inflammatory diseases.