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Increased expression of human calcium-activated chloride channel 1 is correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease

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Chinese Medical Journal 2007年第12期120卷 1051-1057页

作者： WANG Ke FENG Yu-ling WEN Fu-qiang CHEN Xue-rong OU Xue-mei XU Dan YANG Jie DENG Zhi-pin Division of Pulmonary Diseases State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine West China Hospital of Sichuan University Chengdu 610041 China

Background Chronic obstructive pulmonary disease （COPD） is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 （CaCC1） was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC1 and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC1, MUC5AC and mucus in bronchial tissues were examined. Methods Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC1, MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction （RT-PCR）, in situ hybridization with digoxigenin （DIG）-Iabeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff （AB-PAS） staining, respectively. Results Compared with the control group, the stronger expressions of CaCC1 were further detected throughout the bronchial tissues from patients with COPD （P〈0.01）. Furthermore, the stronger expressions of the CaCC1 mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects （P〈0.01） and AB-PAS staining revealed more mucins in COPD patients＇ submucosal gland comparing with that in control subjects （P〈0.01）. Expression levels of the CaCC1 mRNA were respectively negatively correlated with the patients＇ forced expiratory volume in one second （FEV~） / forced vital capacity （FVC） data, FEV1% predicted data, V50% predicted data, V25% predicted data （r=-0.43, r=-0.43, r=-0.35, r=-0.36, P〈0.01, P〈0.01, P〈0.05, P〈0.05）. While the expression levels of the CaCC1 mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands （r=0.39, r=0.46, P〈0

关键词： calcium-activated chloride channel 1 mucin 5AC mucin mucus overproduction chronic obstructive pulmonary disease

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Decreased expression of human aquaporin-5 correlated with mucus overproduction in airways of chronic obstructive pulmonary disease

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Acta Pharmacologica Sinica 2007年第8期28卷 1166-1174页

作者： Ke WANG Yu-lin FENG Fu-qiang WEN~2 Xue-rong CHEN Xue-mei OU Dan XU Jie YANG Zhi-ping DENG Division of Pulmonary Diseases,State Key Laboratory of Biotherapy of China,and Department of Respiratory Medicine,West China Hospital of Sichuan University,Sichuan 610041,China Division of Pulmonary Diseases State Key Laboratory of Biotherapy of Chinaand Department of Respiratory MedicineWest China Hospital of Sichuan UniversitySichuan 610041China

Aim:To investigate the relationship between aquaporin-5(AQP5)expression andmucus overproduction in the airways of Chinese patients with chronic obstruc-tive pulmonary disease(COPD)and the correlation with pulmonary functionchange.Methods:Bronchial tissues were obtained from fiberoptic bronchoscopyand bronchial biopsy in West China Hospital from April to July 2004.Twenty-fivepatients were diagnosed as COPD patients,and another 20 were diagnosed as thecontrol patients.The expressions ofAQP5,mucin 5AC(MUC5AC),and mucin inbronchial tissues were detected by semiquantitative RT-PCR,in situ hybridization,and immunohistochemical and alcian blue-periodic acid-Schiff(AB-PAS)staining,respectively.Results:Compared with the control group,an attenuated expres-sion of AQP5was detected throughout the bronchial tissues from patients withCOPD(P0.05).Simultaneously,increased staining of MUC5AC and mucus in submucosal glandswere noted(Pmucus in submucosal glands in theCOPD groups(P0.05).The decreased expression of AQP5mRNA was correlatedwith forced expiratory volume in 1 s(FEV1)/forced vital capacity(FVC)(r=0.60,P<0.01),FEV1% predicted value(r=0.60,P<0.01),maximal expiratory flow in 50%vital capacity(V50)% predicted value(r=0.55,P<0.01),and maximal expiratory flowin 25% vital capacity(V25)% predicted value(r=0.45,P<0.01).The decreasedexpression was negatively correlated with MUC5AC mRNA of the epitheliumairways(r=-0.45,P<0.01)and the AB-PAS-stained area of submucosal glands(r=-0.61,P<0.01).The upregulation of MUC5AC mRNA correlated with the posi-tively AB-PAS-stained area of submucosal glands and correlated negativelywith FEV1/FVC(r=-0.53;P<0.01),FEV1% predicted value(r=-0.53;P<0.01),V50%predicted value(r=-0.48;P<0.01),and V25% predicted value(r=-0.43;P<0.01).Conclusion:The attenuated gene express

关键词： aquaporin-5 mucin 5AC mucin mucus overproduction chronic obstructive pulmonary disease

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CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma

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Acta Pharmacologica Sinica 2006年第12期27卷 1594-1599页

作者： Hua-hao SHEN~2 Feng XU~2 Gen-sheng ZHANG Shao-bin WANG Wei-hua XU Department of Respiratory Diseases,the Second Affiliated Hospital,Zhejiang University College of Medicine,Hangzhou 310009,China DepartmentofRespiratoryDiseases theSecondAffiliatedHospitalZhejiangUniversityCollegeofMedicineHangzhou310009China

Aim:To explore the effect of a rat anti-mouse CC-chemokine receptor-3(CCR3)monoclonal antibody(CCR3 mAb)on airway eosinophilia and mucus overpro-duction in asthmatic mice.Methods:An asthma model was sensitized and chal-lenged by ovalbumin(OVA)in male C57BL/6 mice.Asthmatic mice were givendual administration(intraperitoneal injection and aerosol inhalation)of CCR3 mAbor nonspecific rat IgG(ns-IgG).The number of total and differential inflammatorycells in the bronchial alveolar lavage fluid(BALF)was counted.Eosinophils number,the goblet cell percentage(GCP)and airway mucus index(AMI)were measured inthe lung tissues.Interleukin(IL)-5 levels in the BALF were examined.The expres-sion of MUC5AC and the epidermal growth factor receptor(EGFR)mRNA in thelung tissues was detected by semi-quantitative RT-PCR.The results were com-pared among the groups.Results:CCR3 mAb significantly suppressed theincreased eosinophils in the BALF and lung tissues in OVA-challenged mice com-pared with ns-IgG-treated mice.IL-5 levels in the BALF in CCR3 mAb and ns-IgGadministration mice exhibited no obvious changes relative to OVA-challengedasthmatic mice.CCR3 mAb reduced the increased GCP and AMI after OVA chal-lenge and decreased the enhanced expression of MUC5AC and EGFR mRNA inlung tissues in asthmatic animals.Conclusion:CCR3 mAb can significantlyinhibit airway eosinophilia and mucus overproduction in asthmatic mice.Block-age of CCR3 may represent a new strategy to asthma therapy.

关键词： asthma CCR3 monoclonal antibody eosinophilic inflammation mucus overproduction MUC5AC epidermal growth factor receptor

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