| Objective: To investigate the mechanism of chronic bronchitis with recurrent long duration infections in the production of MPO anti-neutrophil cytoplasmic antibodies(ANCA).Method: Rats were giving intratracheal injection of LPS and smoking to established chronic bronchitis(CB)model.Rats were given intraperitoneal injection of thioglycolate to induce neutrophil aggregation followed with extraction.Incubated neutrophils with phorbol-12-myristate-13-acetate(PMA)to induce Neutrophil Extracellular Traps(NETs).NETs were then used to immune chronic bronchitis rats.Serum concentrations of myeloperoxidase anti-neutrophil cytoplasmic antibodies(MPO-ANCA),Citrullinated Histone H3(Cit H3),Interferon-a(IFN-a)were evaluated and the pathologic changes of kidneys were observed.Results:(1)The lung pathology of CB rat had the pathological manifestations of chronic bronchitis.(2)The immunofluorescence staining of NETs showed that NETs was a network structure contained DNA,MPO and Cit H3.(3)The serum levels of MPO-ANCA in chronic bronchitis rats immuned with NETs(CB/NETs)were significantly higher than those in chronic bronchitis rats(CB)and healthy control rats,62.4975±19.63764 ng/ml vs17.3806±4.88649 ng/ml,20.8884±4.39607ng/ml(both p<0.01).(4)The serum levels of Cit H3 in CB/NETs rat were significantly higher than those in CB rat and healthy control rats,32.5974±20.2915 ng/ml vs 8.8568±2.36692ng/ml,5.6225±0.83738 ng/ml,(p<0.05,p<0.01).(5)The serum levels of IFN-a were found increased sharply in two CB/NETs rats(3735.7pg/ml,3428.4pg/ml).(6)Serum Cit H3 level showed a positive correlation with serum MPO-ANCA level(r=0.61,P<0.05).(7)Renal function among three groups showed no significant difference yet.(8)The renal and lung pathologies in CB/NETs group had no abnomal changes associated with AAV.Conclusion: Chronic bronchitis with recurrent infections could induce the production of ANCA probably by the stimulation of NETs,but whether it might develop to AAV remains need a duration. |
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