Effects Of CCR3 On Muc5ac In The Airway Of Asthmatic Mice

Part 1 Inflammation and mucus hypersecretion in the airway of asthmatic miceObjective To investigate the inflammation and mucus hypersecretion in airway of asthma mice. Methods Twenty BALB/c mice were randomly devided into two groups: asthma model group (AS group n=10), control group (NS group,n=10). asthmatic model group was sensitized and challenged with ovalbumin (OVA), control group was sensitized and challenged with normal sodium. Total cells and differential inflammatory cells were counted in bronchoalveolar lavage fluid (BALF), the levels of IL-4 and TNF-a in BALF were determined by ELISA, the pathomorphological Changes in the lung were observed by hematoxylin-eosin staining(HE),the goblet cell of airway wall was observed by AB-PAS staining, the expression of Mucin-5ac (Muc5ac) in airway were observed by immunohistochemical staining, the expressions of Muc5ac mRNA in lung tissue were observed by real time fluorescence quantitative reverse transcription polymerase (RT-PCR). Results Total cells, eosinophil, monocytes and lymphocyte cells in BALF, the levels of IL-4,TNF-a in BALF, the hyperplasia of goblet cell in the airway wall, and the expression of Muc5ac in lung tissue of AS group were obviously higher than those in control group(P<0.01 or P<0.05). Conclusions lymphocyte and eosinophil cells obviously observed in the airway inflammation of asthmatic mice which were sensitized and challenged with ovalbumin (OVA). The goblet cell metaplasia and airway mucus hypersecretion were observed in asthmatic mice. They are related closely.Party 2 Effects of CCR3(Chemokine Receptor-3) on Muc5ac in airway of asthmatic mice treated with SB328437Objective To investigate the effects of CCR3 on Muc5ac in the airway of asthmatic mice,And the change which treated with CCR3 antogonist SB328437. Methods Fifty clean BALB/c mice were randomly divided into control group(NS group, n=10),asthmatic group(AS group, n=10), dexamethasone treatment group(AS+DEX, n=10), SB328437 treatment group(AS+SB328437, n=10),vehicle-control(dimethyl sulfoxide,DMSO) group (AS+DMSO,n=10), Total cells and differential inflammatory cells were counted in BALF, the levels of IL-4 and TNF-a in BALF were determined by ELISA,the pathomorphological Changes in the lung were observed by hematoxylin-eosin staining(HE),the goblet cell of airway wall was observed by alcian blue/periodic acid schiff (AB-PAS) staining, the expressions of Mucin 5ac(Muc5ac) and CCR3 in lung tissue were observed by immuneohistochemical staining, the expressions of Muc5ac mRNA and CCR3 mRNA in lung tissue were observed by RT-PCR. Results The total cells, eosinophil, monocytes and lymphocyte cells in BALF, the levels of IL-4,TNF-a in BALF,the goblet cell of airway wall, the expression of Muc5ac and CCR3 positive staining IOD in the airway and the expression of Muc5ac and CCR3 mRNA lung tissue obviously decreased in SB328437 treatment group and DEX treatment group which compared with asthmatic mice model group (P<0.05). Conclusions The current studys suggests that CCR3 may induce airway inflammation,upgrate Muc5ac mRNA and Muc5ac hypersecretion in airway of asthmatic mice. SB328437 may inhibit inflammation and mucus hypersecretion in airway of mice with asthma, which were mediated by CCR3.